BEHAVIORAL AND HORMONAL RESPONSES OF MONKEYS TO FG7142

猴子对 FG7142 的行为和荷尔蒙反应

• 批准号: 7715538
• 负责人: Melinda Ann Novak
• 金额: $ 5.52万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715538
• 关键词: Adult; Agonist; Animals; Anxiety; Behavior; Behavioral; Benzodiazepine Receptor; Benzodiazepines; Blood; Collection; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Data; Dose; Enzyme Immunoassay; FG 7142; Funding; Grant; Hormonal; Hour; Hydrocortisone; Institution; Macaca mulatta; Maintenance; Measures; Monkeys; Pharmaceutical Preparations; Physiological; Plasma; Radioimmunoassay; Reporting; Research; Research Personnel; Resources; Role; Source; Testing; United States National Institutes of Health; Week; design; male; receptor function; response

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们已经提出了焦虑在SIB的启动和维持中的作用。 为了验证这一假设，我们研究了八只成年雄性恒河猴（四只SIB;四只对照）对以混合受试者内设计给予的不同剂量的致焦虑苯二氮卓类（BDZ）反向激动剂FG 7142（溶剂，0.1、0.3、1.0 mg/kg，IM）的激素和行为反应。 所有动物的给药间隔3周。 在处理后15 min收集行为数据，持续1 h，然后立即采血，分别通过酶免疫分析和放射免疫分析进行血浆皮质醇和ACTH分析。 FG 7142的最高剂量显著增加了循环皮质醇浓度（F = 2.98，p <0.05）。 令人惊讶的是，与对照组相比，SIB猴中的皮质醇水平也较高（F = 11.45，p小于0.005）。 ACTH值在不同剂量或组间无显著差异。 尽管已报道FG 7142产生致焦虑行为（例如，增加的抓挠），我们发现在组间或组间给药没有可靠的行为效应。 总之，我们的结果没有发现SIB和对照猴之间BDZ受体功能差异的证据，这些差异将表现为对FG 7142激发的差异反应性。 这些发现并不排除SIB猴子可能会使用其他行为或生理措施表现出焦虑增加的可能性。