Original article| Volume 40, ISSUE 5, P338-352, September 01, 1996

Rearing experience and biogenic amine activity in infant rhesus monkeys

      This paper is only available as a PDF. To read, Please Download here.
      In this report we present evidence that early social experience influences aspects of the function of brain biogenic amine systems, most notably the noradrenergic system. Biogenic amine activity was studied in mother- vs. peer-reared monkey infants over the first 6 months of life and in response to two housing transitions. Norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebrospinal fluid (CSF) were measured. Peer-reared monkeys showed significantly higher CSF levels of norepinephrine and MHPG than mother-reared animals over early development, but showed an attentuated NE response to separation and group formation compared to mother-reared animals. Peer-reared monkeys showed a greater developmental decline in 5-HIAA levels than mother-reared monkeys. There were no rearing effects for DOPAC or HVA over early development; however, peer-reared monkeys showed significantly lower HVA and DOPAC concentrations at 6–8 months of age. The results add to evidence for the influence of primate mothers on the psychobiological development of central nervous system neurotransmitter systems in their infants, and suggest that the noradrenergic system is among the more sensitive of these to early experience.

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


        • Asberg M
        • Nordstrom P
        • Traskman-Bendz L
        Cerebrospinal fluid studies in suicide: An overview.
        Ann N Y Acad Sci. 1986; 487: 243-255
        • Bachevalier J
        Memory loss and socio-emotional disturbances following neonatal damage of the limbic system in monkeys: An animal model of childhood autism.
        in: Tamminga C.A. Shultz S.C. Advances in Neuropsychiatry and Psychopharmacology, Vol. 1, Schizophrenia. Raven Press, New York1991: 129-140
        • Bloom FE
        • Schulman JA
        • Koob GF
        Catecholamines and Behavior.
        in: Trendelenburg U Weiner N Catecholamines II. Springer-Verlag, New York1989: 27-88
        • Brown GL
        • Goodwin FK
        Cerebrospinal fluid correlates of suicide attempts and aggression.
        Ann N Y Acad Sci. 1986; 487: 175-188
        • Champoux M
        • Coe CL
        • Schanberg SM
        • Kuhn CM
        • Suomi SJ
        Hormonal effects of early rearing conditions in the infant rhesus monkey.
        Am J Primatol. 1989; 19: 111-117
        • Charney DS
        • Krystal JJ
        • Southwick SM
        • Nagy LM
        • Woods SW
        • Heninger GR
        Serotonin function in panic and generalized anxiety disorders.
        Psychiatr Ann. 1990; 20: 593-604
        • Charney DS
        • Woods SW
        • Nagy LM
        • Southwick SM
        • Krystal JH
        • Heninger GR
        Noradrenergic function in panic disorder.
        J Clin Psychiatry. 1990; 51: 5-11
        • Clarke AS
        Social rearing effects on HPA axis activity over early development and in response to stress in young rhesus monkeys.
        Dev Psychobiol. 1993; 26: 433-447
        • Clarke AS
        • Wittwer DJ
        • Abbott DH
        • Schneider ML
        Long-term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys.
        Dev Psychobiol. 1994; 27: 257-270
        • Clarke AS
        • Kammerer C
        • George K
        • et al.
        Evidence of heritability of norepinephrine, HVA, and 5-HIAA values in cerebrospinal fluid of rhesus monkeys.
        Biol Psychiatry. 1995; 38: 572-577
        • Cocaro EF
        • Astill JL
        • Szeeley PJ
        • Malkowicz DE
        Serotonin and mood disorders.
        Psychiatr Ann. 1990; 20: 580-586
        • Coe CL
        Psychosocial factors and immunity in nonhuman primates: A review.
        Psychosom Med. 1993; 55: 298-308
        • Coe CL
        • Lubach GR
        • Ershler WB
        • Klopp RG
        Influence of early rearing on lymphocyte proliferation responses in juvenile rhesus monkeys.
        Brain Behav Immun. 1989; 3: 47-60
        • Gibbons RS
        • Hedeker D
        • Waternaux CM
        • Davis JM
        Random regression models: A comprehensive approach to the analysis of longitudinal psychiatric data.
        Psychopharmacol Bull. 1988; 24: 438-443
        • Gibbons RS
        • Hedeker D
        • Elkin I
        • et al.
        Some statistical and conceptual issues in the analysis of longitudinal psychiatric data.
        Arch Gen Psychiatry. 1993; 50: 739-750
        • Goldman-Rakic PS
        Development of cortical circuitry and cognitive function.
        Child Dev. 1987; 58: 601-622
        • Graeff FG
        Neuroanatomy and neurotransmitter regulation of defensive behaviors and related emotions in mammals.
        Braz J Med Biol Res. 1994; 27: 811-829
        • Harlow HF
        • Harlow MK
        • Suomi SJ
        From thought to therapy: Lessons from a primate laboratory.
        Am Scientist. 1971; 59: 538-549
        • Higley JD
        • Suomi SJ
        • Linnoila M
        CSF monoamine metabolite concentrations vary according to age, rearing and sex, and are influenced by the stressor of social separation in rhesus monkeys.
        Psychopharmacology. 1991; 103: 551-556
        • Higley JD
        • Mehlman PT
        • Taub DM
        • et al.
        Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys.
        Arch Gen Psychiatry. 1992; 49: 436-441
        • Higley JD
        • Thompson WT
        • Champoux M
        • et al.
        Paternal and maternal genetic and environmental contributions to CSF monoamine metabolites in rhesus monkeys (Macaca mulatta).
        Arch Gen Psychiatry. 1993; 50: 615-623
        • Hofer MA
        Hidden regulatory processes in early social relationships.
        in: Bateson PG Klopfer PH Social Behavior. Plenum, Berlin1978: 135-166
        • Hofer MA
        Shaping forces within early social relationships.
        in: Krasnegor NA Blass EM Hofer MA Smotherman WP Perinatal Development: A Psychobiological Perspective. Academic Press, New York1987: 251-274
        • Insel TR
        Serotonin in obsessive-compulsive disorder.
        Psychiatr Ann. 1990; 20: 558-559
        • Kapur S
        • Mann JJ
        Role of the dopaminergic system in depression.
        Biol Psychiatry. 1992; 32: 1-17
        • Kostrezawa RM
        Reorganization of noradrenergic neuronal systems following neonatal chemical and surgical injury.
        Prog Brain Res. 1988; 73: 405-423
        • Kraemer GW
        A psychobiological theory of attachment.
        Behav Brain Sci. 1992; 15: 493-511
        • Kraemer GW
        • Clarke AS
        The behavioral neurobiology of self-injurious behavior in rhesus monkeys.
        Prog Neuropsychopharmacol Biol Psychiatry. 1990; 14: S141-S168
        • Kraemer GW
        • McKinney WT
        Interactions of pharmacological agents which alter biogenic amine metabolism and depression: An analysis of contributing factors within a primate model of depression.
        J Affect Disord. 1979; 1: 33-54
        • Kraemer GW
        • Ebert MH
        • Lake CR
        • McKinney WT
        Amphetamine challenge: Effects in previously isolated rhesus monkeys and implications for animal models of schizophrenia.
        in: Miczek KA Ethopharmacology: Primate Models of Neuropsychiatric Disorders. Liss, Orlando1983: 199-218
        • Kraemer GW
        • Ebert MH
        • Schmidt DE
        • McKinney WT
        A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys.
        Neuropsychopharmacology. 1989; 2: 175-189
        • Kraemer GW
        • Ebert MH
        • Schmidt DE
        • McKinney WT
        Strangers in a strange land: A psychobiological study of infant monkeys before and after separation from real or inanimate mothers.
        Child Dev. 1991; 62: 548-566
        • Laird NM
        Missing data in longitudinal studies.
        Stat Med. 1988; 7: 305-315
        • Lapierre YD
        • Ravindran A
        • Bakish D
        Dysthymia and serotonin.
        Int Clin Psychopharmacol. 1993; 8: 87-90
        • Lawlor BA
        Serotonin and Alzheimer's disease.
        Psychiatr Ann. 1990; 20: 567-570
        • Lidow MS
        • Goldman-Rakic PS
        • Rakic P
        Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex.
        Neurobiology. 1991; 88: 10218-10221
        • Lubach GR
        • Kittrell EMW
        • Coe CL
        Maternal influences on body temperature in the infant primate.
        Physiol Behav. 1992; 51: 987-994
        • Marek GJ
        • Seiden LS
        Neurotransmitters in affective disorder.
        in: Archer T Hansen S Behavioral Biology: Neuroendocrine Axis. Lawrence Erlbaum, New York1991: 243-254
        • Matsumoto M
        • Togashi H
        • Yoshioka M
        • Morii K
        • Hirokami M
        • Tochihara M
        • Ikeda T
        • Saito Y
        • Saito H
        Significant correlation between cerebrospinal fluid and brain levels of norepinephrine, serotonin and acetylcholine in anesthesized rats.
        Life Sciences. 1991; 48: 823-829
        • McGuire MT
        • Raleigh MJ
        Serotonin, social behavior, and aggression in vervet monkeys.
        in: Olivier B Mos J Brain PF Ethopharmacology of Agonistic Behaviour in Animals. Martinus Nijhoff Publishers, Hilldale, NJ1987: 207-222
        • Meltzer HY
        • Lowy MT
        The serotonin hypothesis of depression.
        in: Meltzer HY Psychopharmacology: The Third Generation of Progress. Raven Press, Dordrecht, The Netherlands1987: 513-526
        • Plooij FX
        • van de Rijt-Plooij HHC
        Vulnerable periods during infancy: Hierarchically reorganized systems of control, stress, and disease.
        Ethol Sociobiol. 1989; 10: 279-296
        • Post RM
        Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.
        Am J Psychiatry. 1992; 149: 999-1010
        • Rosenblum LA
        • Coplan JD
        • Friedman S
        • Bassoff T
        • Gorman JM
        • Andrews MW
        Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates.
        Biol Psychiatry. 1994; 35: 221-227
        • Schmidt DE
        • Roznoski M
        • Ebert MH
        Qualitative and quantitative high performance liquid chromatographic analysis of monoamine neurotransmitters and metabolites in cerebrospinal fluid and brain tissue using reductive electrochemical detection.
        Biomed Chromatogr. 1990; 4: 215-220
        • Singhal RL
        • Tellner JI
        A perspective: Psychopharmacological aspects of aggression in animals and man.
        Psychiatr J U Ottawa. 1983; 8: 145-153
        • Soubrie P
        Reconciling the role of central serotonin neurons in human and animal behavior.
        Behav Brain Sci. 1986; 9: 319-364
        • Stanley M
        • Stanley B
        • Traskman-Bendz L
        • Mann JJ
        • Meyendorff E
        Neurochemical findings in suicide completers and suicide attempters.
        Suicide Life Threat Behav. 1986; 16: 287-300
        • Sulser F
        Antidepressant treatments and regulation of norepinephrine-receptor-coupled adenylate cyclase systems in brain.
        in: Usdin E. Frontiers in Biochemical and Pharmacological Research in Depression. Raven Press, New York1984: 249-261
        • Sulser F
        New perspectives on the molecular pharmacology of affective disorder.
        Eur Arch Psychiatry Neurol Sci. 1989; 238: 231-239
        • Suomi SJ
        • Harlow HF
        • Domek CJ
        Effect of repetitive infant-infant separation of young monkeys.
        J Abnorm Psychol. 1970; 76: 161-172
        • van Praag HM
        Affective disorders and aggression disorders: Evidence for a common biological mechanism.
        Suicide Life Threat Behav. 1986; 16: 103-133
        • Warburton DM
        Stress and distress in response to change.
        in: Box HO Primate Responses to Environmental Change. Chapman and Hall, New York1991: 351-356
        • Wester P
        • Bergstrom U
        • Eriksson A
        • et al.
        Ventricular cerebrospinal fluid monoamine transmitter and metabolite concentrations reflect human brain neurochemistry in autopsy class.
        J Neurochem. 1990; 11: 48-56
        • Wood JH
        Neurobiology of Cerebrospinal Fluid.
        Plenum Press, London1980