Biogenic amine activity in response to fluoxetine and desipramine in differentially reared rhesus monkeys

Background: It has been hypothesized that adverse early experience may be a mechanism by which children become vulnerable to later psychopathology via alteration of neurochemical or hormonal systems associated with such disor ders, Such effects may in turn affect Eater responses to pharmacologic agen ts that act on these systems, Methods: In this study, 18 mother-reared (MR) and 18 peer-reared (PR) rhesu s monkeys experienced six 1-week separations from cagemates interspersed wi th 1-week reunions, while housed in like-reared groups of 3. Within rearing groups, equal numbers of animals received either fluoxetine (2 mg/kg), des ipramine (5 mg/kg) or placebo delivered daily beginning 4 weeks before the first separation. Levels of norepinephrine (NE), the NE metabolite MHPG, th e dopamine metabolites DOPAC and HVA, and the serotonin metabolite 5HIAA we re measured in CSF samples collected approximately every 2 to 3 weeks durin g these procedures. Results: Following treatment, DMI increased NE and decreased MHPG in the DM I-treated groups, while 5HIAA was decreased in the fluoxetine-treated group s following treatment, The increase in NE was followed by a sharp decline o ver the course of treatment, which was accompanied by an increase in MHPG, The rearing groups did not show a differential response to the drug treatme nts, and the separation manipulation itself had few effects. The mother-rea red group showed higher levels of NE and DOPAC over all samples and higher levels of HVA in most samples. Conclusions: These rearing effects on biogenic amine activity were observed even in the presence of pharmacologic treatments that effectively altered the activity of these systems, and are consistent with previous findings fr om the same subject. The higher NE values observed in mother-reared infants over separations and reunions may have been due to higher basal levels of NE than peer-reared monkeys or to greater responsiveness to the stress of r epeated social disruption or both, These findings agree with other primate studies showing that rearing differences persist beyond the infancy period and add to growing evidence of the important influence of the early social environment on neurobiologic development in primates, (C) 1999 Society of B iological Psychiatry.