Advertisement

Developing a Neurobehavioral Animal Model of Infant Attachment to an Abusive Caregiver

  • Charlis Raineki
    Correspondence
    Address correspondence to Charlis Raineki, Ph.D., Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, Child Study Center, Child and Adolescent Psychiatry, NYU Langone Medical Center, 140 Old Orangeburg Road, Orangeburg, NY 10962
    Affiliations
    Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York

    Child Study Center, Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, New York

    Center for Neural Science, New York University, New York, New York

    Department of Zoology, University of Oklahoma, Norman, Oklahoma
    Search for articles by this author
  • Stephanie Moriceau
    Affiliations
    Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York

    Child Study Center, Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, New York

    Center for Neural Science, New York University, New York, New York

    Department of Zoology, University of Oklahoma, Norman, Oklahoma
    Search for articles by this author
  • Regina M. Sullivan
    Affiliations
    Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York

    Child Study Center, Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, New York

    Center for Neural Science, New York University, New York, New York

    Department of Zoology, University of Oklahoma, Norman, Oklahoma
    Search for articles by this author
Published:February 18, 2010DOI:https://doi.org/10.1016/j.biopsych.2009.12.019

      Background

      Both abused and well cared for infants show attachment to their caregivers, although the quality of that attachment differs. Moreover, the infant's attachment to the abusive caregiver is associated with compromised mental health, especially under stress. In an attempt to better understand how abuse by the caregiver can compromise mental health, we explore the neural basis of attachment in both typical and abusive environments using infant rats, which form attachments to the mother through learning her odor. Here, we hypothesize that the neural circuitry for infant attachment differs based on the quality of the attachment, which can be uncovered during stressful situations.

      Methods

      We used infant rats to compare infant attachment social behaviors and supporting neurobiology using natural maternal odor, as well as two odor-learning attachment paradigms: odor-stroke (mimics typical attachment) and odor-.5 mA shock conditioning (mimics abusive attachment). Next, to uncover differences in behavior and brain, these pups were injected with systemic corticosterone. Finally, pups were reared with an abusive mother to determine ecological relevance.

      Results

      Our results suggest that the natural and learned attachment odors indistinguishably control social behavior in infancy (approach to the odor and interactions with the mother). However, with corticosterone injection, pups with an abusive attachment show disrupted infant social behavior with the mother and engagement of the amygdala.

      Conclusions

      This animal model of attachment accommodates both abusive and typical attachment and suggests that pups' social behavior and underlying neural circuitry may provide clues to understanding attachment in children with various conditions of care.

      Key Words

      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

        • Carlson V.
        • Cicchetti D.
        • Barnett D.
        • Braunwald K.
        Finding order in disorganization: Lessons from research on maltreated infant's attachment to their caregivers.
        in: Cicchetti D. Carlson V. Child Maltreatment: Theory and Research on the Causes and Consequences of Child Abuse and Neglect. Cambrige University Press, New York1989: 494-528
        • Bremner J.D.
        Long-term effects of childhood abuse on brain and neurobiology.
        Child Adolesc Psychiatr Clin N Am. 2003; 12: 271-292
        • Gunnar M.R.
        Integrating neuroscience and psychological approaches in the study of early experiences.
        Ann N Y Acad Sci. 2003; 1008: 238-247
        • Heim C.
        • Nemeroff C.B.
        The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies.
        Biol Psychiatry. 2001; 49: 1023-1039
        • Teicher M.N.
        • Andersen S.L.
        • Polcari A.
        • Andersen C.M.
        • Navalta C.P.
        • Kim D.M.
        The neurobiological consequences of early stress and childhood maltreatment.
        Neurosci Biobehav Rev. 2003; 27: 33-44
        • Kaufman J.
        • Plotsky P.M.
        • Nemeroff C.B.
        • Charney D.S.
        Effects of early adverse experiences on brain structure and function: Clinical implications.
        Biol Psychiatry. 2000; 48: 778-790
        • Leon M.
        Maternal pheromone.
        Physiol Behav. 1974; 13: 441-453
        • Leon M.
        Dietary control maternal pheromone in the lactating rat.
        Physiol Behav. 1975; 14: 311-319
        • Pedersen P.E.
        • Williams C.L.
        • Blass E.M.
        Activation and odor conditioning of suckling behavior in 3-day-old albino rats.
        J Exp Psychol Anim Behav Process. 1982; 8: 329-341
        • Haroutunian V.
        • Campbell B.A.
        Emergence of interoceptive and exteroceptive control of behavior in rats.
        Science. 1979; 205: 927-929
        • Sullivan R.M.
        • Hofer M.A.
        • Brake S.C.
        Olfactory-guided orientation in neonatal rats is enhanced by a conditioned change in behavioral state.
        Dev Psychobiol. 1986; 19: 615-623
        • Sullivan R.M.
        • Wilson D.A.
        • Wong R.
        • Correa A.
        • Leon M.
        Modified behavioral and olfactory bulb responses to maternal odors in preweanling rats.
        Brain Res Dev Brain Res. 1990; 53: 243-247
        • Johanson I.B.
        • Teicher M.H.
        Classical conditioning of an odor preference in 3-day-old rats.
        Behav Neural Biol. 1980; 29: 132-136
        • Sullivan R.M.
        • Taborsky-Barba S.
        • Mendoza R.
        • Itano A.
        • Leon M.
        • Cotman C.W.
        • et al.
        Olfactory classical conditioning in neonates.
        Pediatrics. 1991; 87: 511-518
        • Blozovski D.
        • Cudennec A.
        Passive avoidance learning in the young rat.
        Dev Psychobiol. 1980; 13: 513-518
        • Camp L.L.
        • Rudy J.W.
        Changes in the categorization of appetitive and aversive events during postnatal development of the rat.
        Dev Psychobiol. 1988; 21: 25-42
        • Moriceau S.
        • Sullivan R.M.
        Maternal presence serves as a switch between learning fear and attraction in infancy.
        Nat Neurosci. 2006; 9: 1004-1006
        • Moriceau S.
        • Wilson D.A.
        • Levine S.
        • Sullivan R.M.
        Dual circuitry for odor-shock conditioning during infancy: Corticosterone switches between fear and attraction via amygdala.
        J Neurosci. 2006; 26: 6737-6748
        • Raineki C.
        • Shionoya K.
        • Sander K.
        • Sullivan R.M.
        Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence.
        Learn Mem. 2009; 16: 114-121
        • Roth T.
        • Sullivan R.M.
        Endogenous opioids and their role in odor preference acquisition and consolidation following odor-shock conditioning in infant rats.
        Dev Psychobiol. 2001; 39: 188-198
        • Sullivan R.M.
        • Landers M.
        • Yeaman B.
        • Wilson D.A.
        Good memories of bad events in infancy.
        Nature. 2000; 407: 38-39
        • Roth T.
        • Sullivan R.M.
        Memory of early maltreatment: Neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning.
        Biol Psychiatry. 2005; 57: 823-831
        • Barr G.A.
        Ontogeny of nociception and antinociception.
        NIDA Res Monogr. 1995; 158: 172-201
        • Fitzgerald M.
        The development of nociceptive circuits.
        Nat Rev Neurosci. 2005; 6: 507-520
        • Crittenden P.M.
        Children's strategies for coping with adverse home environments: An interpretation using attachment theory.
        Child Abuse Negl. 1992; 16: 329-343
        • Gunnar M.R.
        • Broderson L.
        • Nachmias M.
        • Buss K.
        • Rigatuso J.
        Stress and attachment security.
        Dev Psychobiol. 1996; 29: 191-204
        • MacDonald H.Z.
        • Beeghly M.
        • Grant-Knight W.
        • Augustyn M.
        • Woods R.W.
        • Cabral H.
        • et al.
        Longitudinal association between infant disorganized attachment and childhood posttraumatic stress symptoms.
        Dev Psychopathol. 2008; 20: 493-508
        • Spangler G.
        • Grossmann K.E.
        Biobehavioral organization in securely and insecurely infants.
        Child Dev. 1992; 64: 1439-14550
        • Sullivan R.M.
        • Wilson D.A.
        The role of norepinephrine in the expression of learned olfactory neurobehavioral responses in infant rats.
        Psychobiology. 1991; 19: 308-312
        • Hofer M.A.
        • Shair H.
        • Singh P.
        Evidence that maternal ventral skin substances promote suckling in infant rats.
        Physiol Behav. 1976; 17: 131-136
        • Teicher M.H.
        • Blass E.M.
        First suckling response of newborn albino rat: The role of olfaction and amniotic fluid.
        Science. 1977; 198: 635-636
        • Avishai-Eliner S.
        • Gilles E.E.
        • Eghbal-Ahmadi M.
        • Bar-El Y.
        • Baram T.Z.
        Altered regulation of gene and protein expression of hypothalamic-pituitary-adrenal axis components in an immature rat model of chronic stress.
        J Neuroendocrinol. 2001; 13: 799-807
        • Gilles E.E.
        • Schultz L.
        • Baram T.Z.
        Abnormal corticosterone regulation in an immature rat model of continuous chronic stress.
        Pediatr Neurol. 1996; 15: 114-119
        • Paxinos G.
        • Tork I.
        • Tecott L.H.
        • Valentino K.L.
        Atlas of the Developing Rat Brain.
        Academic Press, San Diego1991
        • Johnson B.A.
        • Woo C.C.
        • Duong H.
        • Nguyen V.
        • Leon M.
        A learned odor evokes an enhanced Fos-like glomerular response in the olfactory bulb of young rats.
        Brain Res. 1995; 699: 192-200
        • Moriceau S.
        • Shionoya K.
        • Jakubs K.
        • Sullivan R.M.
        Early life stress disrupts attachment learning: The role of amygdala corticosterone, locus coeruleus corticotropin releasing hormone, and olfactory bulb norepinephrine.
        J Neurosci. 2009; 29: 15745-15755
        • Yeh K.Y.
        Corticosterone concentrations in the serum and milk of lactating rats: Parallel changes after induced stress.
        Endocrinology. 1984; 115: 1364-1370
        • Sevelinges Y.
        • Moriceau S.
        • Holman P.
        • Miner C.
        • Muzny K.
        • Gervais R.
        • et al.
        Enduring effects of infant memories: Infant odor-shock conditioning attenuates amygdala activity and adult fear conditioning.
        Biol Psychiatry. 2007; 62: 1070-1079
        • Tyler K.
        • Moriceau S.
        • Sullivan R.M.
        • Greenwood-Van Meerveld B.
        Long-term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock.
        Neurogastroenterol Motil. 2007; 19: 761-768
        • Leon M.
        Neuroethology of olfactory preference development.
        J Neurobiol. 1992; 23: 1557-1573
        • Polan H.J.
        • Hofer M.A.
        Maternally directed orienting behaviors of newborn rats.
        Dev Psychobiol. 1999; 34: 269-279
        • Yuan Q.
        • Harley C.W.
        • Darby-King A.
        • Neve R.L.
        • McLean J.H.
        Early odor preference learning in the rat: Bidirectional effects on cAMP response element-binding protein (CREB) and mutant CREB support a causal role for phosphorylated CREB.
        J Neurosci. 2003; 23: 4760-4765
        • Wilson D.A.
        • Sullivan R.M.
        • Leon M.
        Single-unit analysis of postnatal olfactory learning: Modified olfactory bulb output response patterns to learned attractive odors.
        J Neurosci. 1987; 7: 3154-3162
        • Baron-Cohen S.
        The Essential Difference: Men, Women and the Extreme Male Brain.
        Penguin, London2003
        • Adolphs R.
        • Baron-Cohen S.
        • Tranel D.
        Impaired recognition of social emotions following amygdala damage.
        J Cogn Neurosci. 2002; 14: 1264-1274
        • Amaral D.G.
        The primate amygdala and the neurobiology of social behavior: Implications for understanding social anxiety.
        Biol Psychiatry. 2002; 51: 11-17
        • Fanselow M.S.
        • Gale G.D.
        The amygdala, fear, and memory.
        Ann N Y Acad Sci. 2003; 985: 125-134
        • Phelps E.
        • LeDoux J.
        Contributions of the amygdala to emotions processing: From animal models to human behavior.
        Neuron. 2005; 48: 175-187
        • Amaral D.G.
        • Bauman M.D.
        • Schumann C.M.
        The amygdala and autism: Implications from non-human primate studies.
        Genes Brain Behav. 2003; 2: 295-302
        • Bauman M.D.
        • Lavenex P.
        • Mason W.A.
        • Capitanio J.P.
        • Amaral D.G.
        The development of mother-infant interactions after neonatal amygdala lesions in rhesus monkeys.
        J Neurosci. 2004; 24: 711-721
        • Bauman M.D.
        • Lavenex P.
        • Mason W.A.
        • Capitanio J.P.
        • Amaral D.G.
        The development of social behaviors following neonatal amygdala lesions in rhesus monkeys.
        J Cogn Neurosci. 2004; 16: 1388-1411
        • Bowlby J.
        Attachment.
        Basic Books, New York1965
        • Helfer M.E.
        • Kempe R.S.
        • Krugman R.D.
        The Battered Child.
        University of Chicago Press, Chicago1997
        • Johnson E.O.
        • Kamilaris T.C.
        • Calogero A.E.
        • Gold P.W.
        • Chrousos G.P.
        Effects of early parenting on growth and development in a small primate.
        Pediatr Res. 1996; 39: 999-1005
        • Briere J.
        The long-term clinical correlates of childhood sexual victimization.
        Ann N Y Acad Sci. 1988; 528: 327-334
        • Cirulli F.
        • Francia N.
        • Berry A.
        • Aloe L.
        • Alleva E.
        • Suomi S.J.
        Early life stress a risk factor for mental health: Role of neurotrophins form rodents to non-humans primates.
        Neurosci Biobehav Rev. 2009; 33: 573-585
        • Lupien S.J.
        • McEwen B.S.
        • Gunnar M.R.
        • Heim C.
        Effects of stress throughout the lifespan on the brain, behaviour and cognition.
        Nat Rev Neurosci. 2009; 10: 434-445
        • Sánchez M.M.
        • Ladd C.O.
        • Plotsky P.M.
        Early adverse experience as a developmental risk factor for later psychopathology: Evidence from rodent and primate models.
        Dev Psychopathol. 2001; 13: 419-449
        • Grino M.
        • Paulmyer-Lacroix O.
        • Faudon M.
        • Renard M.
        • Anglade G.
        Blockade of alpha 2-adrenoreceptors stimulates basal and stress-induced adrenocorticotropin secretion in the developing rat through a central mechanism independent from corticotropin-releasing factor and arginine vasopressin.
        Endocinology. 1994; 9: 2549-2557
        • Levine S.
        Plasma free corticosterone response to electric shock in rats stimulated in infancy.
        Science. 1962; 135: 795-796
        • Rosenfeld P.
        • Shchecki D.
        • Levine S.
        Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development.
        Neurosci Biobehav Rev. 1992; 16: 553-568
        • Sapolsky R.M.
        • Meaney M.J.
        Maturation of the adrenocortical stress response: Neuroendocrine control mechanisms and the stress hyporesponsive period.
        Brain Res. 1986; 396: 64-76
        • Bohn M.C.
        Glucocorticoid-induced teratologies of the nervous system.
        in: Yanai J. Neurobehavioral Teratology. Elsevier, New York1984: 365-387
        • Hu Z.
        • Yuri K.
        • Ichikawa T.
        • Kawata M.
        Exposure of neonatal rats to glucocorticoids suppresses the development if choline acetyltransferase-immunreactive neurons: Role of adrenal steroids in the development if forebrain cholinergic neurons.
        J Chem Neuroanat. 1996; 10: 1-10
        • Moriceau S.
        • Raineki C.
        • Holman J.D.
        • Holman J.G.
        • Sullivan R.M.
        Enduring neurobehavioral effects of early life trauma mediated through learning and corticosterone suppression.
        Front Behav Neurosci. 2009; 3: 22
        • Hsu D.T.
        • Chen F.L.
        • Takahashi L.K.
        • Kalin N.H.
        Rapid stress-induced elevations in corticotropin-releasing hormone mRNA in rat central amygdala nucleus and hypothalamic paraventricular nucleus: An in situ hybridization analysis.
        Brain Res. 1998; 788: 305-310
        • Korosi A.
        • Baram T.Z.
        The central corticotropin releasing factor system during development and adulthood.
        Eur J Pharmacol. 2008; 583: 204-214
        • Barr G.A.
        • Moriceau S.
        • Shionoya K.
        • Musny K.
        • Gao P.
        • Wang S.
        • et al.
        Transitions on infant learning are modulated by dopamine in the amygdala.
        Nat Neurosci. 2009; 12: 1367-1369
        • 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
        • Fenoglio K.A.
        • Chen Y.
        • Baram T.Z.
        Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of the stress-regulating brain regions.
        J Neurosci. 2006; 26: 2434-2442
        • Gardner K.L.
        • Hale M.W.
        • Lightman S.L.
        • Plotsky P.M.
        • Lowry C.A.
        Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression.
        Brain Res. 2009; 1305: 47-63
        • Hess E.
        Ethology: An approach to the complete analysis of behavior.
        in: Brown R. Galanter E. Hess E. Mendler G. New Directions in Psychology. Holt, Rinehart and Winston, New York1962: 159-199
        • Fisher A.E.
        The effects of differential early treatment on the social and exploratory behavior of puppies [doctoral dissertation].
        Pennsylvania State University, University Park, PA1955
        • Stanley W.E.
        Differential human handling as reinforcing events and as treatments influencing later social behavior in Basenji puppies.
        Psychol Rep. 1962; 10: 775-788
        • Harlow H.
        • Harlow M.
        The affectional system.
        in: Schrier A. Harlow H. Stollnitz F. Behavior of Non-human Primates. Academic Press, New York1965
        • Suomi S.J.
        Early determinants of behavior: Evidence from primate studies.
        Br Med Bull. 1997; 53: 170-184
        • Rajecki D.
        • Lamb M.
        • Obmascher P.
        Towards a general theory of infantile attachment: A comparative review of aspects of the social bond.
        Behav Brain Sci. 1978; 1: 417-435
        • Hanson J.L.
        • Davidson R.J.
        • Pollak S.D.
        The correlates of early experience on structural brain development.
        Abstr Soc Neurosci. 2009; (Accessed January 27, 2010)
        • Sánchez M.M.
        • Styner M.
        • McCornack K.
        • Graff A.
        • Zhang X.
        • Maestripieri D.
        • et al.
        Decreased left amygdala volume is related to early life stress in an animal model of poor maternal care.
        Abstr Soc Neurosci. 2009; (Accessed January 27, 2010)