BEHAVIORAL AND HORMONAL RESPONSES OF MONKEYS TO FG7142

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have proposed a role for anxiety in the initiation and maintenance of SIB. To test this hypothesis, we investigated hormonal and behavioral responses of eight adult male rhesus macaques (four SIB; four control) to various doses of the anxiogenic benzodiazepine (BDZ) inverse agonist FG 7142 (vehicle, 0.1, 0.3, 1.0 mg/kg, IM) given in a mixed within-subjects design. Treatments were spaced 3 weeks apart for all animals. Behavioral data were collected 15 min post treatment for one hour and then followed immediately by blood collection for plasma cortisol and ACTH analysis by enzyme immunoassay and radioimmunoassay respectively. Circulating cortisol concentrations were significantly increased by the highest dose of FG 7142 (F = 2.98, p less than 0.05). Surprisingly, there was also an overall effect of higher cortisol levels in SIB monkeys compared to controls (F = 11.45, p less than 0.005). ACTH values did not vary significantly by dose or group. Despite the fact that FG 7142 has been reported to produce anxiogenic behaviors (e.g., increased scratching) in rhesus monkeys at the doses used in the present study, we found no reliable behavioral effects of drug administration either across or between groups. In conclusion, our results find no evidence for differences in BDZ receptor function between SIB and control monkeys that would be manifested as differential responsiveness to FG 7142 challenge. These findings do not preclude the possibility that SIB monkeys may show increased anxiety using other behavioral or physiological measures.