BEHAVIORAL AND HORMONAL RESPONSES OF MONKEYS TO FG7142

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们提出了焦虑在SIB的启动和维持中的作用。为了验证这一假设，我们采用混合受试者设计，研究了8只成年雄性恒河猴(4只SIB；4只对照)对不同剂量的焦虑性苯二氮(BDZ)反向激动剂FG7142(Vehicle，0.1，0.3，1.0 mg/kg，IM)的激素和行为反应。所有动物的治疗间隔为3周。用药后15min收集行为学数据，1h后立即采血，分别用酶免疫法和放射免疫法测定血浆皮质醇和ACTH含量。最大剂量的FG7142显著升高循环皮质醇浓度(F=2.98，p<0.05)。令人惊讶的是，与对照组相比，SIB猴子的皮质醇水平也有升高的总体影响(F=11.45p<0.005)。ACTH值在不同剂量或组之间没有显著差异。尽管FG7142已被报道在本研究中使用的剂量下在恒河猴身上产生焦虑行为(例如，更多的抓挠)，但我们发现无论是跨组还是跨组给药都没有可靠的行为影响。总之，我们的结果没有发现SIB和对照猴子之间BDZ受体功能差异的证据，这些差异将表现为对FG7142挑战的不同反应。这些发现并不排除SIB猴子使用其他行为或生理指标表现出更多焦虑的可能性。

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.