Long-term effects of chronic social stress on serotonergic indices in the prefrontal cortex of adult male cynomolgus macaques.

We examined the effects of chronic social stress and social rank on monamine concentrations in the prefrontal cortex (PFC) in adult male cynomolgus macaques (Macaca fascicularis). Seventy-five animals were housed in five-member social groups for 28 months and were exposed to three experimental conditions. A 'no-stress' condition was comprised of animals housed in groups of stable membership throughout the study. Animals assigned to a 'past-stress' condition had their group memberships reorganized at monthly intervals during the first (but not last) 14 months of the study, and a third 'recent-stress' condition consisted of social groups reorganized only during the last 14 months. At necropsy, the brains were collected and frozen at -70 degrees C until analyzed. Prefrontal orbital cortex was assayed for monoamines (serotonin (5-HT), dopamine (DA), norepinephrine (NE)), metabolites (5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG)), and tryptophan using high-performance liquid chromatography with electrochemical detection. Animals in the past-stress condition had significantly lower PFC 5-HIAA concentrations compared to those in the no-stress condition (P < 0.05). PFC 5-HT concentrations of animals in the past-stress condition were significantly lower than those in the no-stress and recent-stress conditions (P < 0.01). The concentrations of DA, HVA, NE and MHPG were not altered. These data suggest that exposure to chronic social stress is associated with long-term selective reductions in serotonergic activity in the PFC. This effect may underlie the association in human beings between reduced serotonergic function and conditions such as pathological grief and posttraumatic stress disorder.