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 disorders. Such effects may in turn affect later responses to pharmacologic agents that act on these systems.


METHODS
In this study, 18 mother-reared (MR) and 18 peer-reared (PR) rhesus monkeys experienced six 1-week separations from cagemates interspersed with 1-week reunions, while housed in like-reared groups of 3. Within rearing groups, equal numbers of animals received either fluoxetine (2 mg/kg), desipramine (5 mg/kg) or placebo delivered daily beginning 4 weeks before the first separation. Levels of norepinephrine (NE), the NE metabolite MHPG, the dopamine metabolites DOPAC and HVA, and the serotonin metabolite 5HIAA were measured in CSF samples collected approximately every 2 to 3 weeks during these procedures.


RESULTS
Following treatment, DMI increased NE and decreased MHPG in the DMI-treated groups, while 5HIAA was decreased in the fluoxetine-treated groups following treatment. The increase in NE was followed by a sharp decline over the course of treatment, which was accompanied by an increase in MHPG. The rearing groups did not show a differential response to the drug treatments, and the separation manipulation itself had few effects. The mother-reared 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 from 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 repeated 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.
Clarke
A S
AS
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.
Ebert
M H
MH
Schmidt
D E
DE
McKinney
W T
WT
Kraemer
G W
GW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D000822:Animal Husbandry / Q000379:methods; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001010:Anxiety, Separation / Q000378:metabolism* / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects*; D001679:Biogenic Amines / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008253:Macaca mulatta / Q000523:psychology; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D011897:Random Allocation; D012931:Social Environment; D013997:Time Factors
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D001679:Biogenic Amines; D005473:Fluoxetine; D015102:3,4-Dihydroxyphenylacetic Acid; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D003891:Desipramine; D006719:Homovanillic Acid