Advertisement

The Serotonin-1A Receptor in Anxiety Disorders

      The serotonin system plays an important role in the neural processing of anxiety. The involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT1A) subtype, in dysfunctional forms of anxiety has been supported by findings from a wide range of preclinical research and clinical trials, including treatment studies, genetic research, and neuroimaging data. The following article summarizes preclinical results with a focus on 5-HT1A receptor knockout and transgenic mice as genetic models of anxiety. Behavioral, autonomic, and endocrinological changes in these mice are reported. This article also presents genetic polymorphisms in humans associated with increased anxiety scores and pharmacological data focused on 5-HT1A receptor agonists and antagonists. Furthermore, molecular neuroimaging results are presented. Recent positron emission tomography (PET) studies have reported reduced 5-HT1A receptor binding in patients with panic disorder and social anxiety disorder, but not in posttraumatic stress disorder. In healthy subjects, increased anxiety scores might be associated with lower 5-HT1A receptor binding. This overview of preclinical and clinical data provides strong evidence for the key role of the 5-HT1A receptor in the serotonergic dysregulation of anxiety disorders.

      Key Words

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

      Purchase one-time access:

      Academic and Personal
      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

        • Arango V.
        • Underwood M.D.
        • Boldrini M.
        • Tamir H.
        • Kassir S.A.
        • Hsiung S.
        • et al.
        Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims.
        Neuropsychopharmacology. 2001; 25: 892-903
        • Lemonde S.
        • Turecki G.
        • Bakish D.
        • Du L.
        • Hrdina P.D.
        • Bown C.D.
        • et al.
        Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide.
        J Neurol Sci. 2003; 23: 8788-8799
        • Barnes N.M.
        • Sharp T.
        A review of central 5-HT receptors and their function.
        Neuropharmacology. 1999; 38: 1083-1152
        • Goldberg H.L.
        • Finnerty R.J.
        The comparative efficacy of buspirone and diazepam in the treatment of anxiety.
        Am J Psychiatry. 1979; 136: 1184-1187
        • Cloninger C.R.
        A systematic method for clinical description and classification of personality variants.
        Arch Gen Psychiatry. 1987; 44: 573-588
        • Bailer U.F.
        • Price J.C.
        • Meltzer C.C.
        • Mathis C.A.
        • Frank G.K.
        • Weissfeld L.
        • et al.
        Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: Relationships to harm avoidance and drive for thinness.
        Neuropsychopharmacology. 2004; 29: 1143-1155
        • Bailer U.F.
        • Frank G.K.
        • Henry S.E.
        • Price J.C.
        • Meltzer C.C.
        • Mathis C.A.
        • et al.
        Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa.
        Biol Psychiatry. 2007; 61: 1090-1099
        • Spindelegger C.
        • Lanzenberger R.
        • Wadsak W.
        • Mien L.K.
        • Stein P.
        • Mitterhauser M.
        • et al.
        Influence of escitalopram treatment on 5-HT(1A) receptor binding in limbic regions in patients with anxiety disorders.
        Mol Psychiatry. 2008; ([published online ahead of print March 25])
        • Sibon I.
        • Benkelfat C.
        • Gravel P.
        • Aznavour N.
        • Costes N.
        • Mzengeza S.
        • et al.
        Decreased [18F]MPPF binding potential in the dorsal raphe nucleus after a single oral dose of fluoxetine: A positron-emission tomography study in healthy volunteers.
        Biol Psychiatry. 2008; 63: 1135-1140
        • Varnas K.
        • Halldin C.
        • Hall H.
        Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain.
        Hum Brain Mapp. 2004; 22: 246-260
        • Witte A.V.
        • Floel A.
        • Stein P.
        • Savli M.
        • Mien L.K.
        • Wadsak W.
        • et al.
        Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects.
        Hum Brain Mapp. 2008; ([published online ahead of print December 11])
        • Drevets W.C.
        • Thase M.E.
        • Moses-Kolko E.L.
        • Price J.
        • Frank E.
        • Kupfer D.J.
        • et al.
        Serotonin-1A receptor imaging in recurrent depression: Replication and literature review.
        Nucl Med Biol. 2007; 34: 865-877
        • Artigas F.
        • Adell A.
        • Celada P.
        Pindolol augmentation of antidepressant response.
        Curr Drug Targets. 2006; 7: 139-147
        • Palchaudhuri M.
        • Flugge G.
        5-HT1A receptor expression in pyramidal neurons of cortical and limbic brain regions.
        Cell Tissue Res. 2005; 321: 159-172
        • Azmitia E.C.
        • Gannon P.J.
        • Kheck N.M.
        • Whitaker-Azmitia P.M.
        Cellular localization of the 5-HT1A receptor in primate brain neurons and glial cells.
        Neuropsychopharmacology. 1996; 14: 35-46
        • Hall H.
        • Lundkvist C.
        • Halldin C.
        • Farde L.
        • Pike V.W.
        • McCarron J.A.
        • et al.
        Autoradiographic localization of 5-HT1A receptors in the post-mortem human brain using [3H]WAY-100635 and [11C]WAY-100635.
        Brain Res. 1997; 745: 96-108
        • Overstreet D.H.
        • Commissaris R.C.
        • De La Garza 2nd, R.
        • File S.E.
        • Knapp D.J.
        • Seiden L.S.
        Involvement of 5-HT1A receptors in animal tests of anxiety and depression: Evidence from genetic models.
        Stress. 2003; 6: 101-110
        • Knapp D.J.
        • Overstreet D.H.
        • Crews F.T.
        Brain 5-HT1A receptor autoradiography and hypothermic responses in rats bred for differences in 8-OH-DPAT sensitivity.
        Brain Res. 1998; 782: 1-10
        • Toth M.
        5-HT1A receptor knockout mouse as a genetic model of anxiety.
        Eur J Pharmacol. 2003; 463: 177-184
        • Bethea C.L.
        • Pau F.K.
        • Fox S.
        • Hess D.L.
        • Berga S.L.
        • Cameron J.L.
        Sensitivity to stress-induced reproductive dysfunction linked to activity of the serotonin system.
        Fertil Steril. 2005; 83: 148-155
        • Lesch K.P.
        Mouse anxiety: The power of knockout.
        Pharmacogenomics J. 2001; 1: 187-192
        • Heisler L.K.
        • Chu H.M.
        • Brennan T.J.
        • Danao J.A.
        • Bajwa P.
        • Parsons L.H.
        • et al.
        Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice.
        Proc Natl Acad Sci U S A. 1998; 95: 15049-15054
        • Parks C.L.
        • Robinson P.S.
        • Sibille E.
        • Shenk T.
        • Toth M.
        Increased anxiety of mice lacking the serotonin1A receptor.
        Proc Natl Acad Sci U S A. 1998; 95 (10734–10734)
        • Ramboz S.
        • Oosting R.
        • Amara D.A.
        • Kung H.F.
        • Blier P.
        • Mendelsohn M.
        • et al.
        Serotonin receptor 1A knockout: An animal model of anxiety-related disorder.
        Proc Natl Acad Sci U S A. 1998; 95: 14476-14781
        • Gross C.
        • Zhuang X.
        • Stark K.
        • Ramboz S.
        • Oosting R.
        • Kirby L.
        • et al.
        Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult.
        Nature. 2002; 416: 396-400
        • Ansorge M.S.
        • Morelli E.
        • Gingrich J.A.
        Inhibition of serotonin but not norepinephrine transport during development produces delayed, persistent perturbations of emotional behaviors in mice.
        J Neurol Sci. 2008; 28: 199-207
        • Ansorge M.S.
        • Zhou M.
        • Lira A.
        • Hen R.
        • Gingrich J.A.
        Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice.
        Science. 2004; 306: 879-881
        • Kusserow H.
        • Davies B.
        • Hortnagl H.
        • Voigt I.
        • Stroh T.
        • Bert B.
        • et al.
        Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin 1A receptors.
        Brain Res Mol Brain Res. 2004; 129: 104-116
        • Gross C.
        • Hen R.
        The developmental origins of anxiety.
        Nat Rev Neurosci. 2004; 5: 545-552
        • Francis D.D.
        • Meaney M.J.
        Maternal care and the development of stress responses.
        Curr Opin Neurobiol. 1999; 9: 128-134
        • Francis D.D.
        • Champagne F.A.
        • Liu D.
        • Meaney M.J.
        Maternal care, gene expression, and the development of individual differences in stress reactivity.
        Ann N Y Acad Sci. 1999; 896: 66-84
        • McEwen B.S.
        Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators.
        Eur J Pharmacol. 2008; 583: 174-185
        • Caspi A.
        • Sugden K.
        • Moffitt T.E.
        • Taylor A.
        • Craig I.W.
        • Harrington H.
        • et al.
        Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene.
        Science. 2003; 301: 386-389
        • Hettema J.M.
        • Prescott C.A.
        • Kendler K.S.
        Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism.
        Am J Psychiatry. 2004; 161: 1581-1587
        • Bienvenu O.J.
        • Hettema J.M.
        • Neale M.C.
        • Prescott C.A.
        • Kendler K.S.
        Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia.
        Am J Psychiatry. 2007; 164: 1714-1721
        • Pattij T.
        • Groenink L.
        • Hijzen T.H.
        • Oosting R.S.
        • Maes R.A.
        • van der Gugten J.
        • et al.
        Autonomic changes associated with enhanced anxiety in 5-HT(1A) receptor knockout mice.
        Neuropsychopharmacology. 2002; 27: 380-390
        • Olivier B.
        • Pattij T.
        • Wood S.J.
        • Oosting R.
        • Sarnyai Z.
        • Toth M.
        The 5-HT(1A) receptor knockout mouse and anxiety.
        Behav Pharmacol. 2001; 12: 439-450
        • Olivier B.
        • Zethof T.
        • Pattij T.
        • van Boogaert M.
        • van Oorschot R.
        • Leahy C.
        • et al.
        Stress-induced hyperthermia and anxiety: Pharmacological validation.
        Eur J Pharmacol. 2003; 463: 117-132
        • Gross C.
        • Santarelli L.
        • Brunner D.
        • Zhuang X.
        • Hen R.
        Altered fear circuits in 5-HT(1A) receptor KO mice.
        Biol Psychiatry. 2000; 48: 1157-1163
        • Groenink L.
        • Van der Gugten J.
        • Verdouw P.M.
        • Maes R.A.
        • Olivier B.
        The anxiolytic effects of flesinoxan, a 5-HT1A receptor agonist, are not related to its neuroendocrine effects.
        Eur J Pharmacol. 1995; 280: 185-193
        • Sibille E.
        • Pavlides C.
        • Benke D.
        • Toth M.
        Genetic inactivation of the serotonin (1A) receptor in mice results in downregulation of major GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety.
        J Neurol Sci. 2000; 20: 2758-2765
        • Lopez J.F.
        • Chalmers D.T.
        • Little K.Y.
        • Watson S.J.
        A.E. Bennett Research Award.
        Biol Psychiatry. 1998; 43: 547-573
        • Wissink S.
        • Meijer O.
        • Pearce D.
        • van Der Burg B.
        • van Der Saag P.T.
        Regulation of the rat serotonin-1A receptor gene by corticosteroids.
        J Biol Chem. 2000; 275: 1321-1326
        • Chalmers D.T.
        • Kwak S.P.
        • Mansour A.
        • Akil H.
        • Watson S.J.
        Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression.
        J Neurol Sci. 1993; 13: 914-923
        • Parsons L.H.
        • Kerr T.M.
        • Tecott L.H.
        5-HT(1A) receptor mutant mice exhibit enhanced tonic, stress-induced and fluoxetine-induced serotonergic neurotransmission.
        J Neurochem. 2001; 77: 607-617
        • Knobelman D.A.
        • Hen R.
        • Lucki I.
        Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse.
        J Pharmacol Exp Ther. 2001; 298: 1083-1091
        • Guilloux J.P.
        • David D.J.
        • Guiard B.P.
        • Chenu F.
        • Reperant C.
        • Toth M.
        • et al.
        Blockade of 5-HT1A receptors by (+/−)-pindolol potentiates cortical 5-HT outflow, but not antidepressant-like activity of paroxetine: Microdialysis and behavioral approaches in 5-HT1A receptor knockout mice.
        Neuropsychopharmacology. 2006; 31: 2162-2172
        • Jolas T.
        • Schreiber R.
        • Laporte A.M.
        • Chastanet M.
        • De Vry J.
        • Glaser T.
        • et al.
        Are postsynaptic 5-HT1A receptors involved in the anxiolytic effects of 5-HT1A receptor agonists and in their inhibitory effects on the firing of serotonergic neurons in the rat?.
        J Pharmacol Exp Ther. 1995; 272: 920-929
        • Olivier B.
        • Soudijn W.
        • van Wijngaarden I.
        The 5-HT1A receptor and its ligands: Structure and function.
        Prog Drug Res. 1999; 52: 103-165
        • Lesch K.P.
        • Mossner R.
        Knockout corner: 5-HT(1A) receptor inactivation: Anxiety or depression as a murine experience.
        Int J Neuropsychopharmacol. 1999; 2: 327-331
        • Collinson N.
        • Dawson G.R.
        On the elevated plus-maze the anxiolytic-like effects of the 5-HT(1A) agonist, 8-OH-DPAT, but not the anxiogenic-like effects of the 5-HT(1A) partial agonist, buspirone, are blocked by the 5-HT1A antagonist, WAY 100635.
        Psychopharmacology (Berl). 1997; 132: 35-43
        • Blier P.
        • Ward N.M.
        Is there a role for 5-HT1A agonists in the treatment of depression?.
        Biol Psychiatry. 2003; 53: 193-203
        • Bandelow B.
        • Zohar J.
        • Hollander E.
        • Kasper S.
        • Möller H.J.
        World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders—first revision.
        World J Biol Psychiatry. 2008; 9: 248-312
        • Coplan J.D.
        • Gorman J.M.
        • Klein D.F.
        Serotonin related functions in panic-anxiety: A critical overview.
        Neuropsychopharmacology. 1992; 6: 189-200
        • Broocks A.
        • Meyer T.
        • Opitz M.
        • Bartmann U.
        • Hillmer-Vogel U.
        • George A.
        • et al.
        5-HT1A responsivity in patients with panic disorder before and after treatment with aerobic exercise, clomipramine or placebo.
        Eur Neuropsychopharmacol. 2003; 13: 153-164
        • Broocks A.
        • Meyer T.
        • Gleiter C.H.
        • Hillmer-Vogel U.
        • George A.
        • Bartmann U.
        • et al.
        Effect of aerobic exercise on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine and to ipsapirone in untrained healthy subjects.
        Psychopharmacology (Berl). 2001; 155: 234-241
        • Kahn R.S.
        • Trestman R.
        • Lawlor B.A.
        • Gabriel S.
        • Davidson M.
        • Siever L.
        Effects of ipsapirone in healthy subjects: A dose–response study.
        Psychopharmacology (Berl). 1994; 114: 155-160
        • Lerer B.
        • Gelfin Y.
        • Gorfine M.
        • Allolio B.
        • Lesch K.P.
        • Newman M.E.
        5-HT1A receptor function in normal subjects on clinical doses of fluoxetine: Blunted temperature and hormone responses to ipsapirone challenge.
        Neuropsychopharmacology. 1999; 20: 628-639
        • Lesch K.P.
        • Rupprecht R.
        • Poten B.
        • Muller U.
        • Sohnle K.
        • Fritze J.
        • et al.
        Endocrine responses to 5-hydroxytryptamine-1A receptor activation by ipsapirone in humans.
        Biol Psychiatry. 1989; 26: 203-205
        • Artigas F.
        • Perez V.
        • Alvarez E.
        Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors.
        Arch Gen Psychiatry. 1994; 51: 248-251
        • Dannon P.N.
        • Sasson Y.
        • Hirschmann S.
        • Iancu I.
        • Grunhaus L.J.
        • Zohar J.
        Pindolol augmentation in treatment-resistant obsessive compulsive disorder: A double-blind placebo controlled trial.
        Eur Neuropsychopharmacol. 2000; 10: 165-169
        • Markovitz P.J.
        • Stagno S.J.
        • Calabrese J.R.
        Buspirone augmentation of fluoxetine in obsessive-compulsive disorder.
        Am J Psychiatry. 1990; 147: 798-800
        • Bell C.J.
        • Nutt D.J.
        Serotonin and panic.
        Br J Psychiatry. 1998; 172: 465-471
        • Pohl R.
        • Balon R.
        • Yeragani V.K.
        • Gershon S.
        Serotonergic anxiolytics in the treatment of panic disorder: A controlled study with buspirone.
        Psychopathology. 1989; 22: 60-67
        • Sheehan D.V.
        • Raj A.B.
        • Sheehan K.H.
        • Soto S.
        Is buspirone effective for panic disorder?.
        J Clin Psychopharmacol. 1990; 10: 3-11
        • Cutler N.R.
        • Hesselink J.M.
        • Sramek J.J.
        A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder.
        Prog Neuropsychopharmacol Biol Psychiatry. 1994; 18: 447-463
        • Lesch K.P.
        5-HT1A receptor responsivity in anxiety disorders and depression.
        Prog Neuropsychopharmacol Biol Psychiatry. 1991; 15: 723-733
        • McDougle C.J.
        • Goodman W.K.
        • Leckman J.F.
        • Holzer J.C.
        • Barr L.C.
        • McCance-Katz E.
        • et al.
        Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder.
        Am J Psychiatry. 1993; 150: 647-649
        • Tauscher J.
        • Bagby R.M.
        • Javanmard M.
        • Christensen B.K.
        • Kasper S.
        • Kapur S.
        Inverse relationship between serotonin 5-HT(1A) receptor binding and anxiety: A [(11)C]WAY-100635 PET investigation in healthy volunteers.
        Am J Psychiatry. 2001; 158: 1326-1328
        • Rabiner E.A.
        • Messa C.
        • Sargent P.A.
        • Husted-Kjaer K.
        • Montgomery A.
        • Lawrence A.D.
        • et al.
        A database of [(11)C]WAY-100635 binding to 5-HT(1A) receptors in normal male volunteers: Normative data and relationship to methodological, demographic, physiological, and behavioral variables.
        Neuroimage. 2002; 15: 620-632
        • Lanzenberger R.R.
        • Mitterhauser M.
        • Spindelegger C.
        • Wadsak W.
        • Klein N.
        • Mien L.K.
        • et al.
        Reduced serotonin-1A receptor binding in social anxiety disorder.
        Biol Psychiatry. 2007; 61: 1081-1089
        • Neumeister A.
        • Bain E.
        • Nugent A.C.
        • Carson R.E.
        • Bonne O.
        • Luckenbaugh D.A.
        • et al.
        Reduced serotonin type 1A receptor binding in panic disorder.
        J Neurol Sci. 2004; 24: 589-591
        • Pike V.W.
        • McCarron J.A.
        • Lammertsma A.A.
        • Osman S.
        • Hume S.P.
        • Sargent P.A.
        • et al.
        Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11 C]WAY-100635.
        Eur J Pharmacol. 1996; 301: R5-R7
        • Farde L.
        • Ito H.
        • Swahn C.G.
        • Pike V.W.
        • Halldin C.
        Quantitative analyses of carbonyl-carbon-11-WAY-100635 binding to central 5-hydroxytryptamine-1A receptors in man.
        J Nucl Med. 1998; 39: 1965-1971
        • Cliffe I.A.
        A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT(1A) receptor PET radioligands.
        Nucl Med. 2000; 27: 441-447
        • Wadsak W.
        • Mien L.
        • Ettlinger D.
        • Lanzenberger R.
        • Haeusler D.
        • Dudczak R.
        • et al.
        Simple and fully automated preparation of [carbonyl-11C]WAY-100635.
        Radiochim Acta. 2007; 95: 417-422
        • Nash J.R.
        • Sargent P.A.
        • Rabiner E.A.
        • Hood S.D.
        • Argyropoulos S.V.
        • Potokar J.P.
        • et al.
        Serotonin 5-HT1A receptor binding in people with panic disorder: Positron emission tomography study.
        Br J Psychiatry. 2008; 193: 229-234
        • Sullivan G.M.
        • Oquendo M.A.
        • Simpson N.
        • Van Heertum R.L.
        • Mann J.J.
        • Parsey R.V.
        Brain serotonin1A receptor binding in major depression is related to psychic and somatic anxiety.
        Biol Psychiatry. 2005; 58: 947-954
        • Bonne O.
        • Bain E.
        • Neumeister A.
        • Nugent A.C.
        • Vythilingam M.
        • Carson R.E.
        • et al.
        No change in serotonin type 1A receptor binding in patients with posttraumatic stress disorder.
        Am J Psychiatry. 2005; 162: 383-385
        • Moses-Kolko E.L.
        • Price J.C.
        • Thase M.E.
        • Meltzer C.C.
        • Kupfer D.J.
        • Mathis C.A.
        • et al.
        Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635.
        Synapse. 2007; 61: 523-530
        • Sargent P.A.
        • Kjaer K.H.
        • Bench C.J.
        • Rabiner E.A.
        • Messa C.
        • Meyer J.
        • et al.
        Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: Effects of depression and antidepressant treatment.
        Arch Gen Psychiatry. 2000; 57: 174-180
        • Bhagwagar Z.
        • Rabiner E.A.
        • Sargent P.A.
        • Grasby P.M.
        • Cowen P.J.
        Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635.
        Mol Psychiatry. 2004; 9: 386-392
        • Lesch K.P.
        • Gutknecht L.
        Focus on the 5-HT1A receptor: Emerging role of a gene regulatory variant in psychopathology and pharmacogenetics.
        Int J Neuropsychopharmacol. 2004; 7: 381-385
        • Lesch K.P.
        Molecular foundation of anxiety disorders.
        J Neural Transm. 2001; 108: 717-746
        • Coplan J.D.
        • Lydiard R.B.
        Brain circuits in panic disorder.
        Biol Psychiatry. 1998; 44: 1264-1276
        • Santana N.
        • Bortolozzi A.
        • Serrats J.
        • Mengod G.
        • Artigas F.
        Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex.
        Cereb Cortex. 2004; 14: 1100-1109
        • Amargos-Bosch M.
        • Bortolozzi A.
        • Puig M.V.
        • Serrats J.
        • Adell A.
        • Celada P.
        • et al.
        Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex.
        Cereb Cortex. 2004; 14: 281-299
        • Puig M.V.
        • Artigas F.
        • Celada P.
        Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: Involvement of serotonin and GABA.
        Cereb Cortex. 2005; 15: 1-14
        • Diaz-Mataix L.
        • Scorza M.C.
        • Bortolozzi A.
        • Toth M.
        • Celada P.
        • Artigas F.
        Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: Role in atypical antipsychotic action.
        J Neurol Sci. 2005; 25: 10831-10843
        • Sarnyai Z.
        • Sibille E.L.
        • Pavlides C.
        • Fenster R.J.
        • McEwen B.S.
        • Toth M.
        Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin (1A) receptors.
        Proc Natl Acad Sci U S A. 2000; 97: 14731-14736
        • Zhuang X.
        • Gross C.
        • Santarelli L.
        • Compan V.
        • Trillat A.C.
        • Hen R.
        Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors.
        Neuropsychopharmacology. 1999; 21: 52S-60S
        • Klemenhagen K.C.
        • Gordon J.A.
        • David D.J.
        • Hen R.
        • Gross C.T.
        Increased fear response to contextual cues in mice lacking the 5-HT1A receptor.
        Neuropsychopharmacology. 2006 Jan; 31: 101-111