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Carol A. Shively, PhD; David P. Friedman, PhD; H. Donald Gage, PhD; Michael C. Bounds, BA; Clive Brown-Proctor, PhD; Joseph B. Blair, PhD; Jessica A. Henderson, PhD; Michael A. Smith, BS; Nancy Buchheimer, BS, CNMT

Arch Gen Psychiatry. 2006;63:396-403.

Context  Current animal models of depression are inadequate to further our understanding of depression. New models that allow for analysis of cognitive function and sex differences are needed.

Objective  To characterize serotonin 1A (5-HT_1A) receptor binding potential (BP) and its relationship with specific characteristics of behavioral depression in cynomolgus monkeys.

Design  A 23-month case-control study.

Setting  Small social groups in the laboratory.

Subjects  Seventeen adult female cynomolgus monkeys.

Main Outcome Measures  Serotonin 1A receptor BP was examined by positron emission tomography using the radioligand 4,2"-(methoxyphenyl)-1-[2"-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine in the raphe, amygdala, hippocampus, and anterior cingulate cortex in monkeys characterized by behavioral observation as depressed or not depressed. Aggression, submission, affiliation, pathologic behaviors, and activity levels were determined by behavioral observation. Heart rate and hypothalamic-pituitary-adrenal function were also determined.

Results  Throughout the brain areas examined, there was a reduction in 5-HT_1A BP in depressed monkeys. The 5-HT_1A BP in the amygdala and hippocampus was associated with aggression and submission. Friendly interaction, grooming, and locomotion were associated with 5-HT_1A BP in the left cingulate cortex, whereas attention directed toward the environment was associated with 5-HT_1A BP in the right cingulate cortex. The 5-HT_1A receptor BP was inversely associated with heart rate in the raphe, left cingulate, and right amygdala.

Conclusions  This is the fourth in a series of studies that suggest that depressive behavior in adult female cynomolgus monkeys is similar to that observed in humans. It has been observed in 2 large groups of monkeys randomly selected from feral populations, suggesting that the capacity for depression is inherent in the species. This animal model holds promise to further our understanding of the basic mechanisms of affective behavior, the neuropathophysiologic characteristics of depression and the cognitive dysfunction that accompanies them, genetic and environmental factors that may affect depression risk, and the role of reproductive function in the excess depression risk in women.

Author Affiliations: Departments of Pathology (Comparative Medicine) (Dr Shively), Physiology and Pharmacology (Dr Friedman), and Radiology (Drs Gage, Brown-Proctor, and Blair and Mr Bounds and Ms Buchheimer), and Program in Integrative Neuroscience (Dr Henderson and Mr Smith), Wake Forest University School of Medicine, Winston-Salem, NC.

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