Effects of rearing condition on HPA axis response to fluoxetine and desipramine treatment over repeated social separations in young rhesus monkeys.
Normal hypothalamic-pituitary-adrenal (HPA) axis activity is disrupted in several types of human psychiatric disorders, and has been widely reported to be altered as a result of early experience in rodents. In this study the effects of early social experience on later response of the HPA axis to separations from cagemates and pharmacologic treatments were examined in rhesus monkeys. HPA axis activity was measured in mother-reared and peer-reared monkey infants in conjunction with six repeated separations from and reunions with their cagemates. Within each rearing group, infants were assigned to one of three treatment groups that received continuous treatment with either fluoxetine (2 mg/kg), desipramine (DMI, 5 mg/kg) or placebo (saline) beginning 2 weeks prior to separations. At 2 weeks after drug treatment, fluoxetine increased ACTH and cortisol in the treated groups, while DMI decreased ACTH and cortisol in both treated groups; however, these effects were not persistent over the separations. While these treatment effects tended to be more pronounced in the mother-reared group, the rearing groups did not show a clearly differential response to either of the treatments. The most prominent finding was that mother-reared monkeys showed significantly higher ACTH and cortisol levels than peer-reared monkeys over all samples, an effect that may have mitigated a potential rearing group difference in treatment response. The results add to growing evidence for the influence of primate mothers on the functional development of psychobiological systems in their infants, and suggest that the HPA axis is among the more sensitive of these systems to postnatal experience.
Asher Center for the Study and Treatment of Depressive Disorders, Department of Psychiatry and Behavioral Sciences, Northwestern University Medical School, Chicago, IL 60611-3008, USA. sclarke@nwu.edu
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Clarke
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Kraemer
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Kupfer
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001010:Anxiety, Separation / Q000188:drug therapy / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone; D003891:Desipramine / Q000494:pharmacology*; D003907:Dexamethasone; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D005938:Glucocorticoids; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D009769:Object Attachment; D010379:Peer Group; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012931:Social Environment; D012934:Social Isolation / Q000523:psychology
D000928:Antidepressive Agents; D005938:Glucocorticoids; D005473:Fluoxetine; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003891:Desipramine; D006854:Hydrocortisone