Advertisement

The Central Amygdala as an Integrative Hub for Anxiety and Alcohol Use Disorders

  • Nicholas W. Gilpin
    Correspondence
    Address correspondence to Nicholas W. Gilpin, Ph.D., Department of Physiology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112
    Affiliations
    Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

    Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana
    Search for articles by this author
  • Melissa A. Herman
    Affiliations
    Committee on the Neurobiology of Addictive Disorders (MAH, MR), The Scripps Research Institute, La Jolla, California
    Search for articles by this author
  • Marisa Roberto
    Affiliations
    Committee on the Neurobiology of Addictive Disorders (MAH, MR), The Scripps Research Institute, La Jolla, California
    Search for articles by this author
Published:September 20, 2014DOI:https://doi.org/10.1016/j.biopsych.2014.09.008

      Abstract

      The central amygdala (CeA) plays a central role in physiologic and behavioral responses to fearful stimuli, stressful stimuli, and drug-related stimuli. The CeA receives dense inputs from cortical regions, is the major output region of the amygdala, is primarily GABAergic (inhibitory), and expresses high levels of prostress and antistress peptides. The CeA is also a constituent region of a conceptual macrostructure called the extended amygdala that is recruited during the transition to alcohol dependence. We discuss neurotransmission in the CeA as a potential integrative hub between anxiety disorders and alcohol use disorder, which are commonly co-occurring in humans. Imaging studies in humans and multidisciplinary work in animals collectively suggest that CeA structure and function are altered in individuals with anxiety disorders and alcohol use disorder, the end result of which may be disinhibition of downstream “effector” regions that regulate anxiety-related and alcohol-related behaviors.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Shin L.M.
        • Liberzon I.
        The neurocircuitry of fear, stress, and anxiety disorders.
        Neuropsychopharmacology. 2010; 35: 169-191
        • Cheng D.T.
        • Knight D.C.
        • Smith C.N.
        • Helmstetter F.J.
        Human amygdala activity during the expression of fear responses.
        Behav Neurosci. 2006; 120: 1187-1195
        • Cheng D.T.
        • Knight D.C.
        • Smith C.N.
        • Stein E.A.
        • Helmstetter F.J.
        Functional MRI of human amygdala activity during Pavlovian fear conditioning: Stimulus processing vs response expression.
        Behav Neurosci. 2003; 117: 3-10
        • Semple W.E.
        • Goyer P.F.
        • McCormick R.
        • Donovan B.
        • Muzic Jr, R.F.
        • Rugle L.
        • et al.
        Higher brain blood flow at amygdala and lower frontal cortex blood flow in PTSD patients with comorbid cocaine and alcohol abuse compared with normals.
        Psychiatry. 2000; 63: 65-74
        • Morey R.A.
        • Dolcos F.
        • Petty C.M.
        • Cooper D.A.
        • Hayes J.P.
        • Labar K.S.
        • et al.
        The role of trauma-related distractors on neural systems for working memory and emotion processing in posttraumatic stress disorder.
        J Psychiatr Res. 2009; 43: 809-817
        • Dickie E.W.
        • Brunet A.
        • Akerib V.
        • Armony J.L.
        An fMRI investigation of memory encoding in PTSD: Influence of symptom severity.
        Neuropsychologia. 2008; 46: 1522-1531
        • Rauch S.L.
        • Whalen P.J.
        • Shin L.M.
        • McInerney S.C.
        • Macklin M.L.
        • Lasko N.B.
        • et al.
        Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study.
        Biol Psychiatry. 2000; 47: 769-776
        • Nitschke J.B.
        • Sarinopoulos I.
        • Oathes D.J.
        • Johnstone T.
        • Whalen P.J.
        • Davidson R.J.
        • et al.
        Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.
        Am J Psychiatry. 2009; 166: 302-310
        • Whalen P.J.
        • Johnstone T.
        • Somerville L.H.
        • Nitschke J.B.
        • Polis S.
        • Alexander A.L.
        • et al.
        A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder.
        Biol Psychiatry. 2008; 63: 858-863
        • Tillfors M.
        • Furmark T.
        • Marteinsdottir I.
        • Fischer H.
        • Pissiota A.
        • Langstrom B.
        • et al.
        Cerebral blood flow in subjects with social phobia during stressful speaking tasks: A PET study.
        Am J Psychiatry. 2001; 158: 1220-1226
        • Straube T.
        • Mentzel H.J.
        • Miltner W.H.
        Neural mechanisms of automatic and direct processing of phobogenic stimuli in specific phobia.
        Biol Psychiatry. 2006; 59: 162-170
        • Wright C.I.
        • Martis B.
        • McMullin K.
        • Shin L.M.
        • Rauch S.L.
        Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia.
        Biol Psychiatry. 2003; 54: 1067-1076
        • van den Heuvel O.A.
        • Veltman D.J.
        • Groenewegen H.J.
        • Witter M.P.
        • Merkelbach J.
        • Cath D.C.
        • et al.
        Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis.
        Arch Gen Psychiatry. 2005; 62: 922-933
        • Domschke K.
        • Ohrmann P.
        • Braun M.
        • Suslow T.
        • Bauer J.
        • Hohoff C.
        • et al.
        Influence of the catechol-O-methyltransferase val158met genotype on amygdala and prefrontal cortex emotional processing in panic disorder.
        Psychiatry Res. 2008; 163: 13-20
        • Hershon H.I.
        Alcohol withdrawal symptoms: phenomenology and implications.
        Br J Addict Alcohol Other Drugs. 1973; 68: 295-302
        • Driessen M.
        • Meier S.
        • Hill A.
        • Wetterling T.
        • Lange W.
        • Junghanns K.
        The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders.
        Alcohol Alcohol. 2001; 36: 249-255
        • Willinger U.
        • Lenzinger E.
        • Hornik K.
        • Fischer G.
        • Schonbeck G.
        • Aschauer H.N.
        • et al.
        Anxiety as a predictor of relapse in detoxified alcohol-dependent patients.
        Alcohol Alcohol. 2002; 37: 609-612
        • Koob G.F.
        • Volkow N.D.
        Neurocircuitry of addiction.
        Neuropsychopharmacology. 2010; 35: 217-238
        • Kiefer F.
        • Wiedemann K.
        Neuroendocrine pathways of addictive behavior.
        Addict Biol. 2004; 9: 205-212
        • Wrase J.
        • Makris N.
        • Braus D.F.
        • Mann K.
        • Smolka M.N.
        • Kennedy D.N.
        • et al.
        Amygdala volume associated with alcohol abuse relapse and craving.
        Am J Psychiatry. 2008; 165: 1179-1184
        • Zhang L.
        • Kerich M.
        • Schwandt M.L.
        • Rawlings R.R.
        • McKellar J.D.
        • Momenan R.
        • et al.
        Smaller right amygdala in Caucasian alcohol-dependent male patients with a history of intimate partner violence: A volumetric imaging study.
        Addict Biol. 2013; 18: 537-547
        • Yan P.
        • Li C.S.
        Decreased amygdala activation during risk taking in non-dependent habitual alcohol users: A preliminary fMRI study of the stop signal task.
        Am J Drug Alcohol Abuse. 2009; 35: 284-289
        • Hill S.Y.
        • De Bellis M.D.
        • Keshavan M.S.
        • Lowers L.
        • Shen S.
        • Hall J.
        • et al.
        Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism.
        Biol Psychiatry. 2001; 49: 894-905
        • Glahn D.C.
        • Lovallo W.R.
        • Fox P.T.
        Reduced amygdala activation in young adults at high risk of alcoholism: Studies from the Oklahoma family health patterns project.
        Biol Psychiatry. 2007; 61: 1306-1309
        • Schacht J.P.
        • Anton R.F.
        • Myrick H.
        Functional neuroimaging studies of alcohol cue reactivity: A quantitative meta-analysis and systematic review.
        Addict Biol. 2013; 18: 121-133
        • Fryer S.L.
        • Jorgensen K.W.
        • Yetter E.J.
        • Daurignac E.C.
        • Watson T.D.
        • Shanbhag H.
        • et al.
        Differential brain response to alcohol cue distractors across stages of alcohol dependence.
        Biol Psychol. 2012; 92: 282-291
        • Alheid G.F.
        • Heimer L.
        New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: The striatopallidal, amygdaloid, and corticopetal components of substantia innominata.
        Neuroscience. 1988; 27: 1-39
        • Krettek J.E.
        • Price J.L.
        A description of the amygdaloid complex in the rat and cat with observations on intra-amygdaloid axonal connections.
        J Comp Neurol. 1978; 178: 255-280
        • Dong H.W.
        • Petrovich G.D.
        • Watts A.G.
        • Swanson L.W.
        Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain.
        J Comp Neurol. 2001; 436: 430-455
        • Koob G.F.
        A role for brain stress systems in addiction.
        Neuron. 2008; 59: 11-34
        • Gilpin N.W.
        • Roberto M.
        Neuropeptide modulation of central amygdala neuroplasticity is a key mediator of alcohol dependence.
        Neurosci Biobehav Rev. 2012; 36: 873-888
        • Sakanaka M.
        • Shibasaki T.
        • Lederis K.
        Distribution and efferent projections of corticotropin-releasing factor-like immunoreactivity in the rat amygdaloid complex.
        Brain Res. 1986; 382: 213-238
        • Duvarci S.
        • Pare D.
        Amygdala microcircuits controlling learned fear.
        Neuron. 2014; 82: 966-980
        • LeDoux J.E.
        • Cicchetti P.
        • Xagoraris A.
        • Romanski L.M.
        The lateral amygdaloid nucleus: Sensory interface of the amygdala in fear conditioning.
        J Neurosci. 1990; 10: 1062-1069
        • Tully K.
        • Li Y.
        • Tsvetkov E.
        • Bolshakov V.Y.
        Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses.
        Proc Natl Acad Sci U S A. 2007; 104: 14146-14150
        • McDonald A.J.
        Cortical pathways to the mammalian amygdala.
        Prog Neurobiol. 1998; 55: 257-332
        • Johansen J.P.
        • Cain C.K.
        • Ostroff L.E.
        • LeDoux J.E.
        Molecular mechanisms of fear learning and memory.
        Cell. 2011; 147: 509-524
        • Bernard J.F.
        • Huang G.F.
        • Besson J.M.
        Nucleus centralis of the amygdala and the globus pallidus ventralis: Electrophysiological evidence for an involvement in pain processes.
        J Neurophysiol. 1992; 68: 551-569
        • Neugebauer V.
        • Galhardo V.
        • Maione S.
        • Mackey S.C.
        Forebrain pain mechanisms.
        Brain Res Rev. 2009; 60: 226-242
        • Ehrlich I.
        • Humeau Y.
        • Grenier F.
        • Ciocchi S.
        • Herry C.
        • Lüthi A.
        Amygdala inhibitory circuits and the control of fear memory.
        Neuron. 2009; 62: 757-771
        • McDonald A.J.
        Immunohistochemical identification of gammaaminobutyric acid-containing neurons in the rat basolateral amygdala.
        Neurosci Lett. 1985; 53: 203-207
        • Nitecka L.
        • Ben-Ari Y.
        Distribution of GABA-like immunoreactivity in the rat amygdaloid complex.
        J Comp Neurol. 1987; 266: 45-55
        • Pitkänen A.
        • Stefanacci L.
        • Farb C.R.
        • Go G.G.
        • LeDoux J.E.
        • Amaral D.G.
        Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus.
        J Comp Neurol. 1995; 356: 288-310
        • Savander V.
        • Go C.G.
        • LeDoux J.E.
        • Pitkänen A.
        Intrinsic connections of the rat amygdaloid complex: Projections originating in the basal nucleus.
        J Comp Neurol. 1995; 361: 345-368
        • Royer S.
        • Martina M.
        • Paré D.
        An inhibitory interface gates impulse traffic between the input and output stations of the amygdala.
        J Neurosci. 1999; 19: 10575-10583
        • Le Gal La Salle G.
        • Paxinos G.
        • Emson P.
        • Ben-Ari Y.
        Neurochemical mapping of GABAergic systems in the amygdaloid complex and bed nucleus of the stria terminalis.
        Brain Res. 1978; 155: 397-403
        • McDonald A.J.
        • Augustine J.R.
        Localization of GABA-like immunoreactivity in the monkey amygdala.
        Neuroscience. 1993; 52: 281-294
        • Paré D.
        • Smith Y.
        Distribution of GABA immunoreactivity in the amygdaloid complex of the cat.
        Neuroscience. 1993; 57: 1061-1076
        • Pape H.C.
        • Pare D.
        Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear.
        Physiol Rev. 2010; 90: 419-463
        • Pitkänen A.
        Connectivity of the rat amygdaloid complex.
        in: Aggleton J.P. The Amygdala. Oxford University Press, New York2000
        • Hopkins D.A.
        • Holstege G.
        Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat.
        Exp Brain Res. 1978; 32: 529-547
        • Penzo M.A.
        • Robert V.
        • Li B.
        Fear conditioning potentiates synaptic transmission onto long-range projection neurons in the lateral subdivision of central amygdala.
        J Neurosci. 2014; 34: 2432-2437
        • Tye K.M.
        • Prakash R.
        • Kim S.Y.
        • Fenno L.E.
        • Grosenick L.
        • Zarabi H.
        • et al.
        Amygdala circuitry mediating reversible and bidirectional control of anxiety.
        Nature. 2011; 471: 358-362
        • DeFelipe J.
        • López-Cruz P.L.
        • Benavides-Piccione R.
        • Bielza C.
        • Larrañaga P.
        • Anderson S.
        • et al.
        New insights into the classification and nomenclature of cortical GABAergic interneurons.
        Nat Rev Neurosci. 2013; 14: 202-216
        • Kubota Y.
        • Shigematsu N.
        • Karube F.
        • Sekigawa A.
        • Kato S.
        • Yamaguchi N.
        • et al.
        Selective coexpression of multiple chemical markers defines discrete populations of neocortical GABAergic neurons.
        Cereb Cortex. 2011; 21: 1803-1817
        • Alheid G.F.
        • Beltramino C.A.
        • De Olmos J.S.
        • Forbes M.S.
        • Swanson D.J.
        • Heimer L.
        The neuronal organization of the supracapsular part of the stria terminalis in the rat: The dorsal component of the extended amygdala.
        Neuroscience. 1998; 84: 967-996
        • Cook C.J.
        Glucocorticoid feedback increases the sensitivity of the limbic system to stress.
        Physiol Behav. 2002; 75: 455-464
        • Kolber B.J.
        • Roberts M.S.
        • Howell M.P.
        • Wozniak D.F.
        • Sands M.S.
        • Muglia L.J.
        Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning.
        Proc Natl Acad Sci U S A. 2008; 105: 12004-12009
        • Gozzi A.
        • Jain A.
        • Giovannelli A.
        • Bertollini C.
        • Crestan V.
        • Schwarz A.J.
        • et al.
        A neural switch for active and passive fear.
        Neuron. 2010; 67: 656-666
        • Senn V.
        • Wolff S.B.
        • Herry C.
        • Grenier F.
        • Ehrlich I.
        • Gründemann J.
        • et al.
        Long-range connectivity defines behavioral specificity of amygdala neurons.
        Neuron. 2014; 81: 428-437
        • LeDoux J.E.
        • Iwata J.
        • Cicchetti P.
        • Reis D.J.
        Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear.
        J Neurosci. 1988; 8: 2517-2529
        • Rizvi T.A.
        • Ennis M.
        • Behbehani M.M.
        • Shipley M.T.
        Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: Topography and reciprocity.
        J Comp Neurol. 1991; 303: 121-131
        • Gray T.S.
        • Magnuson D.J.
        Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat.
        Peptides. 1992; 13: 451-460
        • Oliveira M.A.
        • Prado W.A.
        Role of PAG in the antinociception evoked from the medial or central amygdala in rats.
        Brain Res Bull. 2001; 54: 55-63
        • Xu W.
        • Lundeberg T.
        • Wang Y.T.
        • Li Y.
        • Yu L.-C.
        Antinociceptive effects of calcitonin gene-related peptide in the central nucleus of the amygdala: Activating opioid receptors through amygdala-periaqueductal gray pathway.
        Neuroscience. 2003; 118: 1015-1022
        • Johansen J.P.
        • Tarpley J.W.
        • LeDoux J.E.
        • Blair H.T.
        Neural substrates for expectation-modulated fear learning in the amygdala and periaqueductal gray.
        Nat Neurosci. 2010; 13: 979-986
        • Kornetsky C.
        • Esposito R.U.
        Euphorigenic drugs: Effects on the reward pathways of the brain.
        Fed Proc. 1979; 38: 2473-2476
        • Tsumori T.
        • Yokota S.
        • Qin Y.
        • Oka T.
        • Yasui Y.
        A light and electron microscopic analysis of the convergent insular cortical and amygdaloid projections to the posterior lateral hypothalamus in the rat, with special reference to cardiovascular function.
        Neurosci Res. 2006; 56: 261-269
        • Kokkinidis L.
        • Borowski T.B.
        Sensitization of mesolimbic brain stimulation reward after electrical kindling of the amygdala.
        Brain Res Bull. 1991; 27: 791-796
        • Beaulieu S.
        • Paolo T.D.
        • Barden N.
        Participation of the central amygdaloid nucleus in the response of adrenocorticotropin secretion to immobilization stress: opposing roles of the noradrenergic and dopaminergic systems.
        Neuroendocrinology. 1987; 45: 37-46
        • Gray T.S.
        • Carney M.E.
        • Magnuson D.J.
        Direct projections from the central amygdaloid nucleus to the hypothalamic paraventricular nucleus: Possible role in stress-induced adrenocorticotropin release.
        Neuroendocrinology. 1989; 50: 433-446
        • Tsubouchi K.
        • Tsumori T.
        • Yokota S.
        • Okunishi H.
        • Yasui Y.
        A disynaptic pathway from the central amygdaloid nucleus to the paraventricular hypothalamic nucleus via the parastrial nucleus in the rat.
        Neurosci Res. 2007; 59: 390-398
        • Petrov T.
        • Krukoff T.L.
        • Jhamandas J.H.
        Convergent influence of the central nucleus of the amygdala and the paraventricular hypothalamic nucleus upon brainstem autonomic neurons as revealed by c-fos expression and anatomical tracing.
        J Neurosci Res. 1995; 42: 835-845
        • Feldman S.
        • Weidenfeld J.
        The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41.
        Brain Res Bull. 1998; 45: 389-393
        • Xu Y.
        • Day T.A.
        • Buller K.M.
        The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1β administration.
        Neuroscience. 1999; 94: 175-183
        • Amaral D.G.
        • Sinnamon H.M.
        The locus coeruleus: Neurobiology of a central noradrenergic nucleus.
        Prog Neurobiol. 1977; 9: 147-196
        • Cedarbaum J.M.
        • Aghajanian G.K.
        Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique.
        J Comp Neurol. 1978; 178: 1-16
        • Reyes B.A.
        • Carvalho A.F.
        • Vakharia K.
        • van Bockstaele E.J.
        Amygdalar peptidergic circuits regulating noradrenergic locus coeruleus neurons: Linking limbic and arousal centers.
        Exp Neurol. 2011; 230: 96-105
        • Valentino R.J.
        • van Bockstaele E.V.
        Convergent regulation of locus coeruleus activity as an adaptive response to stress.
        Eur J Pharmacol. 2008; 583: 194-203
        • Smith R.J.
        • Aston-Jones G.
        Noradrenergic transmission in the extended amygdala: Role in increased drug-seeking and relapse during protracted drug abstinence.
        Brain Struct Funct. 2008; 213: 43-61
        • Koob G.F.
        Corticotropin-releasing factor, norepinephrine, and stress.
        Biol Psychiatry. 1999; 46: 1167-1180
        • Lechner S.M.
        • Valentino R.J.
        Glucocorticoid receptor-immunoreactivity in corticotrophin-releasing factor afferents to the locus coeruleus.
        Brain Res. 1999; 816: 17-28
        • Danielsen E.H.
        • Magnuson D.J.
        • Gray T.S.
        The central amygdaloid nucleus innervation of the dorsal vagal complex in rat: A Phaseolus vulgaris leucoagglutinin lectin anterograde tracing study.
        Brain Res Bull. 1989; 22: 705-715
        • Saha S.
        • Batten T.F.C.
        • Henderson Z.
        A GABAergic projection from the central nucleus of the amygdala to the nucleus of the solitary tract: A combined anterograde tracing and electron microscopic immunohistochemical study.
        Neuroscience. 2000; 99: 613-626
        • Roozendaal B.
        • Koolhaas J.M.
        • Bohus B.
        Central amygdala lesions affect behavioral and autonomic balance during stress in rats.
        Physiol Behav. 1991; 50: 777-781
        • Baklavadzhyan O.G.
        • Pogosyan N.L.
        • Arshakyan A.V.
        • Darbinyan A.G.
        • Khachatryan A.V.
        • Nikogosyan T.G.
        Studies of the role of the central nucleus of the amygdala in controlling cardiovascular functions.
        Neurosci Behav Physiol. 2000; 30: 231-236
        • LaBar K.S.
        • Gatenby J.C.
        • Gore J.C.
        • LeDoux J.E.
        • Phelps E.A.
        Human amygdala activation during conditioned fear acquisition and extinction: A mixed-trial fMRI study.
        Neuron. 1998; 20: 937-945
        • Whalen P.J.
        • Rauch S.L.
        • Etcoff N.L.
        • McInerney S.C.
        • Lee M.B.
        • Jenike M.A.
        Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.
        J Neurosci. 1998; 18: 411-418
        • Liberzon I.
        • Sripada C.S.
        The functional neuroanatomy of PTSD: A critical review.
        Prog Brain Res. 2008; 167: 151-169
        • Rosenkranz J.A.
        • Venheim E.R.
        • Padival M.
        Chronic stress causes amygdala hyperexcitability in rodents.
        Biol Psychiatry. 2010; 67: 1128-1136
        • Ventura-Silva A.P.
        • Melo A.
        • Ferreira A.C.
        • Carvalho M.M.
        • Campos F.L.
        • Sousa N.
        • Pêgo J.M.
        Excitotoxic lesions in the central nucleus of the amygdala attenuate stress-induced anxiety behavior.
        Front Behav Neurosci. 2013; 7: 32
        • Edwards S.
        • Baynes B.B.
        • Carmichael C.Y.
        • Zamora-Martinez E.R.
        • Barrus M.
        • Koob G.F.
        • Gilpin N.W.
        Traumatic stress reactivity promotes excessive alcohol drinking and alters the balance of prefrontal cortex-amygdala activity.
        Trans Psychiatry. 2013; 3: e296
        • Wilensky A.E.
        • Schafe G.E.
        • LeDoux J.E.
        Functional inactivation of the amygdala before but not after auditory fear conditioning prevents memory formation.
        J Neurosci. 1999; 19: RC48
        • Pare D.
        • Quirk G.J.
        • LeDoux J.E.
        New vistas on amygdala networks in conditioned fear.
        J Neurophysiol. 2004; 92: 1-9
        • Pascoe J.P.
        • Kapp B.S.
        Electrophysiological characteristics of amygdaloid central nucleus neurons during Pavlovian fear conditioning in the rabbit.
        Behav Brain Res. 1985; 16: 117-133
        • Ciocchi S.
        • Herry C.
        • Grenier F.
        • Wolff S.B.
        • Letzkus J.J.
        • Vlachos I.
        • et al.
        Encoding of conditioned fear in central amygdala inhibitory circuits.
        Nature. 2010; 468: 277-282
        • Andero R.
        • Dias B.G.
        • Ressler K.J.
        A role for Tac2, NkB, and Nk3 receptor in normal and dysregulated fear memory consolidation.
        Neuron. 2014; 83: 444-454
        • Duvarci S.
        • Popa D.
        • Paré D.
        Central amygdala activity during fear conditioning.
        J Neurosci. 2011; 31: 289-294
        • Li H.
        • Penzo M.A.
        • Taniguchi H.
        • Kopec C.D.
        • Huang Z.J.
        • Li B.
        Experience-dependent modification of a central amygdala fear circuit.
        Nat Neurosci. 2013; 16: 332-339
        • Amir A.
        • Amano T.
        • Paré D.
        Physiological identification and infralimbic responsiveness of rat intercalated amygdala neurons.
        J Neurophysiol. 2011; 105: 3054-3066
        • Sierra-Mercado D.
        • Padilla-Coreano N.
        • Quirk G.J.
        Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear.
        Neuropsychopharmacology. 2011; 36: 529-538
        • Amano T.
        • Unal C.T.
        • Paré D.
        Synaptic correlates of fear extinction in the amygdala.
        Nat Neurosci. 2010; 13: 489-494
        • Sotres-Bayon F.
        • Quirk G.J.
        Prefrontal control of fear: More than just extinction.
        Curr Opin Neurobiol. 2010; 20: 231-235
        • Weiner J.L.
        • Valenzuela C.F.
        Ethanol modulation of GABAergic transmission: The view from the slice.
        Pharmacol Ther. 2006; 111: 533-554
        • Zhu P.J.
        • Lovinger D.M.
        Ethanol potentiates GABAergic synaptic transmission in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala.
        J Neurophysiol. 2006; 96: 433-441
        • Peters J.
        • Kalivas P.W.
        • Quirk G.J.
        Extinction circuits for fear and addiction overlap in prefrontal cortex.
        Learn Mem. 2009; 16: 279-288
        • Gass J.T.
        • Trantham-Davidson H.
        • Kassab A.S.
        • Glen Jr, W.B.
        • Olive M.F.
        • Chandler L.J.
        Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.
        J Neurosci. 2014; 34: 7562-7574
        • Belelli D.
        • Harrison N.L.
        Extrasynaptic GABA A receptors: Form, pharmacology, and function.
        J Neurosci. 2009; 29: 12757-12763
        • Glykys J.
        • Mody I.
        Activation of GABA A receptors: Views from outside the synaptic cleft.
        Neuron. 2007; 56: 763-770
        • Semyanov A.
        • Walker M.C.
        • Kullmann D.M.
        • Silver R.A.
        Tonically active GABA A receptors: Modulating gain and maintaining the tone.
        Trends Neurosci. 2004; 27: 262-269
        • Jia F.
        • Chandra D.
        • Homanics G.E.
        • Harrison N.L.
        Ethanol modulates synaptic and extrasynaptic GABA A receptors in the thalamus.
        J Pharmacol Exp Ther. 2008; 326: 475-482
        • Mody I.
        • Glykys J.
        • Wei W.
        A new meaning for “Gin & Tonic”: Tonic inhibition as the target for ethanol action in the brain.
        Alcohol. 2007; 41: 145-153
        • Roberto M.
        • Madamba S.G.
        • Moore S.D.
        • Tallent M.K.
        • Siggins G.R.
        Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons.
        Proc Natl Acad Sci U S A. 2003; 100: 2053-2058
        • Roberto M.
        • Madamba S.G.
        • Stouffer D.G.
        • Parsons L.H.
        • Siggins G.R.
        Increased GABA release in the central amygdala of ethanol-dependent rats.
        J Neurosci. 2004; 24: 10159-10166
        • Herman M.A.
        • Contet C.
        • Justice N.J.
        • Vale W.
        • Roberto M.
        Subunit-specific tonic GABA currents and differential effects of ethanol within the central amygdala circuitry of CRF1 reporter mice.
        J Neurosci. 2013; 33: 3284-3298
        • Hill S.Y.
        • De Bellis M.D.
        • Keshavan M.S.
        • Lowers L.
        • Shen S.
        • Hall J.
        • Pitts T.
        Right amygdala volume in adolescent and young adult offspring from families at high risk for developing alcoholism.
        Biol Psychiatry. 2001; 49: 894-905
        • O’Daly O.G.
        • Trick L.
        • Scaife J.
        • Marshall J.
        • Ball D.
        • Phillips M.L.
        • et al.
        Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism.
        Neuropsychopharmacology. 2012; 37: 2267-2276
        • Breese G.R.
        • Knapp D.J.
        • Overstreet D.H.
        Stress sensitization of ethanol withdrawal-induced reduction in social interaction: inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist.
        Neuropsychopharmacology. 2004; 29: 470-482
        • O’Dell L.E.
        • Roberts A.J.
        • Smith R.T.
        • Koob G.F.
        Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure.
        Alcohol Clin Exp Res. 2004; 28: 1676-1682
        • Breese G.R.
        • Overstreet D.H.
        • Knapp D.J.
        Conceptual framework for the etiology of alcoholism: A “kindling”/stress hypothesis.
        Psychopharmacology. 2005; 178: 367-380
        • Gilpin N.W.
        • Richardson H.N.
        • Cole M.
        • Koob G.F.
        Vapor inhalation of alcohol in rats.
        Curr Protoc Neurosci Chapter 9:Unit. 2008; 9: 29
        • Roberto M.
        • Cruz M.T.
        • Gilpin N.W.
        • Sabino V.
        • Schweitzer P.
        • Bajo M.
        • et al.
        Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence.
        Biol Psychiatry. 2010; 67: 831-839
        • Roberto M.
        • Gilpin N.W.
        • O’Dell L.E.
        • Cruz M.T.
        • Morse A.C.
        • Siggins G.R.
        • et al.
        Cellular and behavioral interactions of gabapentin with alcohol dependence.
        J Neurosci. 2008; 28: 5762-5771
        • Jacobsen L.K.
        • Southwick S.M.
        • Kosten T.R.
        Substance use disorders in patients with posttraumatic stress disorder: A review of the literature.
        Am J Psychiatry. 2001; 158: 1184-1190
        • Yehuda R.
        • Brand S.
        • Yang R.K.
        Plasma neuropeptide Y concentrations in combat exposed veterans: Relationship to trauma exposure, recovery from PTSD, and coping.
        Biol Psychiatry. 2006; 59: 660-663
        • Ressler K.J.
        • Mercer K.B.
        • Bradley B.
        • Jovanovic T.
        • Mahan A.
        • Kerley K.
        • et al.
        Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor.
        Nature. 2011; 470: 492-497
        • Rassnick S.
        • Heinrichs S.C.
        • Britton K.T.
        • Koob G.F.
        Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal.
        Brain Res. 1993; 605: 25-32
        • Heilig M.
        • McLeod S.
        • Brot M.
        • Heinrichs S.C.
        • Menzaghi F.
        • Koob G.F.
        Anxiolytic-like action of neuropeptide Y: Mediation by Y1 receptors in amygdala, and dissociation from food intake effects.
        Neuropsychopharmacology. 1993; 8: 357-363
        • Gutman A.R.
        • Yang Y.
        • Ressler K.J.
        • Davis M.
        The role of neuropeptide Y in the expression and extinction of fear-potentiated startle.
        J Neurosci. 2008; 28: 12682-12690
        • Liang K.C.
        • Melia K.R.
        • Miserendino M.J.
        • Falls W.A.
        • Campeau S.
        • Davis M.
        Corticotropin-releasing factor: Long-lasting facilitation of the acoustic startle reflex.
        J Neurosci. 1992; 12: 2303-2312
        • Walker D.L.
        • Miles L.A.
        • Davis M.
        Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses.
        Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33: 1291-1308
        • Iwasaki-Sekino A.
        • Mano-Otagiri A.
        • Ohata H.
        • Yamauchi N.
        • Shibasaki T.
        Gender differences in corticotropin and corticosterone secretion and corticotropin-releasing factor mRNA expression in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala in response to footshock stress or psychological stress in rats.
        Psychoneuroendocrinology. 2009; 34: 226-237
        • Ciccocioppo R.
        • de Guglielmo G.
        • Hansson A.C.
        • Ubaldi M.
        • Kallupi M.
        • Cruz M.T.
        • Oleata C.S.
        • Heilig M.
        • Roberto M.
        Restraint stress alters nociceptin/orphanin FQ and CRF systems in the rat central amygdala: significance for anxiety-like behaviors.
        J Neurosci. 2014; 34: 363-372
        • Pitts M.W.
        • Todorovic C.
        • Blank T.
        • Takahashi L.K.
        The central nucleus of the amygdala and corticotropin-releasing factor: Insights into contextual fear memory.
        J Neurosci. 2009; 29: 7379-7388
        • Sajdyk T.J.
        • Fitz S.D.
        • Shekhar A.
        The role of neuropeptide Y in the amygdala on corticotropin-releasing factor receptor-mediated behavioral stress responses in the rat.
        Stress. 2006; 9: 21-28
        • Cohen H.
        • Liu T.
        • Kozlovsky N.
        • Kaplan Z.
        • Zohar J.
        • Mathé A.A.
        The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder.
        Neuropsychopharmacology. 2012; 37: 350-363
        • Adamec R.
        • Fougere D.
        • Risbrough V.
        CRF receptor blockade prevents initiation and consolidation of stress effects on affect in the predator stress model of PTSD.
        Int J Neuropsychopharmacol. 2010; 13: 747-757
        • McDonald A.J.
        Coexistence of somatostatin with neuropeptide Y, but not with cholecystokinin or vasoactive intestinal peptide, in neurons of the rat amygdala.
        Brain Res. 1989; 500: 37-45
        • Justice N.J.
        • Yuan Z.F.
        • Sawchenko P.E.
        • Vale W.
        Type 1 corticotropin-releasing factor receptor expression reported in BAC transgenic mice: Implications for reconciling ligand-receptor mismatch in the central corticotropin-releasing factor system.
        J Comp Neurol. 2008; 511: 479-496
        • Nie Z.
        • Schweitzer P.
        • Roberts A.J.
        • Madamba S.G.
        • Moore S.D.
        • Siggins G.R.
        Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors.
        Science. 2004; 303: 1512-1514
        • Merlo-Pich E.
        • Lorang M.
        • Yeganeh M.
        • Rodriguez de Fonseca F.
        • Raber J.
        • Koob G.
        • Weiss F.
        Increase of extracellular corticotrophin-releasing factor-like immunoreactivity levels in the amygdale of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis.
        J Neurosci. 1995; 15: 5439-5447
        • Chu K.
        • Koob G.F.
        • Cole M.
        • Zorrilla E.P.
        • Roberts A.J.
        Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF1 receptor antagonist antalarmin and by CRF1 receptor knockout.
        Pharmacol Biochem Behav. 2007; 86: 813-821
        • Funk C.K.
        • Zorrilla E.P.
        • Lee M.-J.
        • Rice K.C.
        • Koob G.F.
        Corticotropin-releasing factor-1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats.
        Biol Psychiatry. 2007; 61: 78-86
        • Funk C.K.
        • O’Dell L.E.
        • Crawford E.F.
        • Koob G.F.
        Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats.
        J Neurosci. 2006; 26: 11324-11332
        • Lowery-Gionta E.G.
        • Navarro M.
        • Li C.
        • Pleil K.E.
        • Rinker J.A.
        • Cox B.R.
        • et al.
        Corticotropin releasing factor signaling in the central amygdala is recruited during binge-like ethanol consumption in C57BL/6J mice.
        J Neurosci. 2012; 32: 3405-3413
        • Cippitelli A.
        • Damadzic R.
        • Singley E.
        • Thorsell A.
        • Ciccocioppo R.
        • Eskay R.L.
        • et al.
        Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats.
        Pharmacol Biochem Behav. 2012; 100: 522-529
        • Lowery E.G.
        • Spanos M.
        • Navarro M.
        • Lyons A.M.
        • Hodge C.W.
        • Thiele T.E.
        CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis.
        Neuropsychopharmacology. 2010; 35: 1241-1252
        • Sparta D.R.
        • Sparrow A.M.
        • Lowery E.G.
        • Fee J.R.
        • Knapp D.J.
        • Thiele T.E.
        Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures.
        Alcohol Clin Exp Res. 2008; 32: 259-265
        • Waselus M.
        • Nazzaro C.
        • Valentino R.J.
        • Van Bockstaele E.J.
        Stress-induced redistribution of corticotropin-releasing factor receptor subtypes in the dorsal raphe nucleus.
        Biol Psychiatry. 2009; 66: 76-83
        • Haubensak W.
        • Kunwar P.S.
        • Cai H.
        • Ciocchi S.
        • Wall N.R.
        • Ponnusamy R.
        • et al.
        Genetic dissection of an amygdala microcircuit that gates conditioned fear.
        Nature. 2010; 468: 270-276
        • Gilpin N.W.
        • Misra K.
        • Herman M.A.
        • Cruz M.T.
        • Koob G.F.
        • Roberto M.
        Neuropeptide Y opposes alcohol effects on gamma-aminobutyric acid release in amygdala and blocks the transition to alcohol dependence.
        Biol Psychiatry. 2011; 69: 1091-1099
        • Roy A.
        • Pandey S.C.
        The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure.
        Alcohol Clin Exp Res. 2002; 26: 796-803
        • Eva C.
        • Mele P.
        • Collura D.
        • Nai A.
        • Pisu M.G.
        • Serra M.
        • Biggio G.
        Modulation of neuropeptide Y and Y1 receptor expression in the amygdala by fluctuations in the brain content of neuroactive steroids during ethanol drinking discontinuation in Y1R/LacZ transgenic mice.
        J Neurochem. 2008; 104: 1043-1054
        • Sparrow A.M.
        • Lowery-Gionta E.G.
        • Pleil K.E.
        • Li C.
        • Sprow G.M.
        • Cox B.R.
        • et al.
        Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J mice via Y1 and Y2 receptors.
        Neuropsychopharmacology. 2012; 37: 1409-1421
        • Gilpin N.W.
        • Misra K.
        • Koob G.F.
        Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced decreases in alcohol drinking.
        Pharmacol Biochem Behav. 2008; 90: 475-480
        • Overstreet D.H.
        • Knapp D.J.
        • Breese G.R.
        Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors.
        Pharmacol Biochem Behav. 2003; 77: 405-413
        • Huang M.M.
        • Overstreet D.H.
        • Knapp D.J.
        • Angel R.
        • Wills T.A.
        • Navarro M.
        • et al.
        Corticotropin-releasing factor (CRF) sensitization of ethanol withdrawal-induced anxiety-like behavior is brain site specific and mediated by CRF-1 receptors: Relation to stress-induced sensitization.
        J Pharmacol Exp Ther. 2010; 332: 298-307
        • Kallupi M.
        • Vendruscolo L.F.
        • Carmichael C.Y.
        • George O.
        • Koob G.F.
        • Gilpin N.W.
        Neuropeptide Y Y2 R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats.
        Addict Biol. 2014; 19: 755-757
        • Hershon H.I.
        Alcohol withdrawal symptoms and drinking behavior.
        J Stud Alcohol. 1977; 38: 953-971
        • Becker H.C.
        • Lopez M.F.
        • Doremus-Fitzwater T.L.
        Effects of stress on alcohol drinking: A review of animal studies.
        Psychopharmacology. 2011; 218: 131-156
        • Logrip M.L.
        • Zorrilla E.P.
        • Koob G.F.
        Stress modulation of drug self-administration: Implications for addiction comorbidity with post-traumatic stress disorder.
        Neuropharmacology. 2012; 62: 552-564
        • Meyer E.M.
        • Long V.
        • Fanselow M.S.
        • Spigelman I.
        Stress increases voluntary alcohol intake, but does not alter established drinking habits in a rat model of posttraumatic stress disorder.
        Alcohol Clin Exp Res. 2013; 37: 566-574
        • Enoch M.A.
        • Goldman D.
        Genetics of alcoholism and substance abuse.
        Psychiatr Clin North Am. 1999; 22: 289-299
        • Treutlein J.
        • Kissling C.
        • Frank J.
        • Wiemann S.
        • Dong L.
        • Depner M.
        • et al.
        Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples.
        Mol Psychiatry. 2006; 11: 594-602
        • Hansson A.C.
        • Cippitelli A.
        • Sommer W.H.
        • Fedeli A.
        • Björk K.
        • Soverchia L.
        • et al.
        Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress.
        Proc Natl Acad Sci U S A. 2006; 103: 15236-15241
        • Hansson A.C.
        • Cippitelli A.
        • Sommer W.H.
        • Ciccocioppo R.
        • Heilig M.
        Region-specific down-regulation of Crhr1 gene expression in alcohol-preferring msP rats following ad lib access to alcohol.
        Addict Biol. 2007; 12: 30-34
        • Herman M.A.
        • Kallupi M.
        • Luu G.
        • Oleata C.S.
        • Heilig M.
        • Koob G.F.
        • et al.
        Enhanced GABAergic transmission in the central nucleus of the amygdala of genetically selected Marchigian Sardinian rats: alcohol and CRF effects.
        Neuropharmacology. 2013; 67: 337-348
        • Liu X.
        • Weiss F.
        Additive effect of stress and drug cues on reinstatement of ethanol seeking: Exacerbation by history of dependence and role of concurrent activation of corticotropin-releasing factor and opioid mechanisms.
        J Neurosci. 2002; 22: 7856-7861
        • Cippitelli A.
        • Damadzic R.
        • Hansson A.C.
        • Singley E.
        • Sommer W.H.
        • Eskay R.
        Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking.
        Psychopharmacology. 2010; 208: 417-426
        • Herman J.P.
        • Figueiredo H.
        • Mueller N.K.
        • Ulrich-Lai Y.
        • Ostrander M.M.
        • Choi D.C.
        • Cullinan W.E.
        Central mechanisms of stress integration: Hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness.
        Front Neuroendocrinol. 2003; 24: 151-180
        • Herman J.P.
        • Mueller N.K.
        • Figueiredo H.
        Role of GABA and glutamate circuitry in hypothalamo-pituitary-adrenocortical stress integration.
        Ann N Y Acad Sci. 2004; 1018: 35-45
        • Adinoff B.
        • Krebaum S.R.
        • Chandler P.A.
        • Ye W.
        • Brown M.B.
        • Williams M.J.
        Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness.
        Alcohol Clin Exp Res. 2005; 29: 517-527
        • Lovallo W.R.
        • Dickensheets S.L.
        • Myers D.A.
        • Thomas T.L.
        • Nixon S.J.
        Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men.
        Alcohol Clin Exp Res. 2000; 24: 651-658
        • Richardson H.N.
        • Lee S.Y.
        • O’Dell L.E.
        • Koob G.F.
        • Rivier C.L.
        Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state.
        Eur J Neurosci. 2008; 28: 1641-1653
        • Vendruscolo L.F.
        • Barbier E.
        • Schlosburg J.E.
        • Misra K.K.
        • Whitfield Jr, T.W.
        • et al.
        Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.
        J Neurosci. 2012; 32: 7563-7571
        • Lachize S.
        • Apostolakis E.M.
        • van der Laan S.
        • Tijssen A.M.
        • Xu J.
        • de Kloet E.R.
        • Meijer O.C.
        Steroid receptor coactivator-1 is necessary for regulation of corticotropin-releasing hormone by chronic stress and glucocorticoids.
        Proc Natl Acad Sci U S A. 2009; 106: 8038-8042
        • van der Laan S.
        • Lachize S.B.
        • Vreugdenhil E.
        • de Kloet E.R.
        • Meijer O.C.
        Nuclear receptor coregulators differentially modulate induction and glucocorticoid receptor-mediated repression of the corticotropin-releasing hormone gene.
        Endocrinology. 2008; 149: 725-732
        • Lesscher H.M.
        • McMahon T.
        • Lasek A.W.
        • Chou W.H.
        • Connolly J.
        • Kharazia V.
        • et al.
        Amygdala protein kinase C epsilon regulates corticotropin-releasing factor and anxiety-like behavior.
        Genes Brain Behav. 2008; 7: 323-333
        • Lesscher H.M.
        • Wallace M.J.
        • Zeng L.
        • Wang V.
        • Deitchman J.K.
        • McMahon T.
        • et al.
        Amygdala protein kinase C epsilon controls alcohol consumption.
        Genes Brain Behav. 2009; 8: 493-499
        • Bajo M.
        • Cruz M.T.
        • Siggins G.R.
        • Messing R.
        • Roberto M.
        Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala.
        Proc Natl Acad Sci U S A. 2008; 105: 8410-8415
        • Qi Z.H.
        • Song M.
        • Wallace M.J.
        • Wang D.
        • Newton P.M.
        • McMahon T.
        • et al.
        Protein kinase C{epsilon} regulates {gamma}-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of {gamma}2 subunits.
        J Biol Chem. 2007; 282: 33052-33063
        • Cruz M.T.
        • Bajo M.
        • Maragnoli M.E.
        • Tabakoff B.
        • Siggins G.R.
        • Roberto M.
        Type 7 adenylyl cyclase is involved in the ethanol and CRF sensitivity of GABAergic synapses in mouse central amygdala.
        Front Neurosci. 2011; 4: 207
        • Kuo D.Y.
        • Yang S.F.
        • Chu S.C.
        • Chen C.H.
        • Chen P.N.
        • Hsieh Y.S.
        The effect of protein kinase C-delta knockdown on anti-free radical enzyme and neuropeptide Y gene expression in phenylpropanolamine-treated rats.
        J Neurochem. 2010; 114: 1217-1230
        • Cozzoli D.K.
        • Courson J.
        • Caruana A.L.
        • Miller B.W.
        • Greentree D.I.
        • Thompson A.B.
        • et al.
        Nucleus accumbens mGluR5-associated signaling regulates binge alcohol drinking under drinking-in-the-dark procedures.
        Alcohol Clin Exp Res. 2012; 36: 1623-1633
        • Cozzoli D.K.
        • Goulding S.P.
        • Zhang P.W.
        • Xiao B.
        • Hu J.H.
        • Ary A.W.
        • et al.
        Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: Functional implications for alcoholism.
        J Neurosci. 2009; 29: 8655-8668