Abstract # 153:

Scheduled for Friday, June 22, 2007 05:00 PM-07:00 PM: Session 14 (South Main Hall) Poster Presentation

5-HT1A Receptor Binding is Increased in the Hippocampus of Depressed Cynomolgus Macaques (Macaca fascicularis)

E. J. Glover1, S. L. Willard2, A. T. Davenport3, J. Thompson2, D. P. Friedman3, J. D. Higley4, P. B. DePetrillo3, E. Singley4 and C. A. Shively2
1Wake Forest University School of Medicine, Neuroscience Program, Winston-Salem, NC 27157, USA, 2Pathology (Comparative Medicine), Wake Forest University School of Medicine, 3Physiology & Pharmacology, Wake Forest University School of Medicine, 4National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
     Post-mortem studies suggest that depressed patients may have perturbations in 5-HT1A receptor binding in hippocampus. However, results are inconsistent and may be confounded by variability in drug exposure and tissue handling. Here, 5-HT1A receptor binding was determined in the hippocampus of depressed and nondepressed adult females. Time spent in depressed behavior (slumped or collapsed body posture accompanied by a lack of responsiveness to environmental stimuli to which other monkeys are attending, and open eyes) was recorded in females housed in stable social groups (n=4 each group) using scan sampling once weekly for 26 months. Subjects were behaviorally characterized as depressed (n=6) or nondepressed (n=6). Heart rate was recorded via telemetry and basal cortisol was measured. 5-hydroxyindoleacetic acid (5HIAA) was measured in cerebrospinal fluid (CSF). Following necropsy, 20 µm coronal sections of hippocampus were collected from each animal. [3H]MPPF and phosphor imaging plates were used to assess receptor binding. Alpha levels were set at p<0.05; all tests were two-sided. On average, 5-HT1A binding was higher in all hippocampal fields in depressed compared to nondepressed monkeys. ANOVA revealed these differences to be significant in CA4. Pearson r correlations revealed significant associations between 5-HT1A binding and basal cortisol, 24 hour heart rate, and CSF 5-HIAA. These data suggest that, like human beings, depressed cynomolgus macaques exhibit disrupted serotonin neurotransmission. Funded by MH5688, GM6424, and The John D. and Catherine T. McArthur Foundation.