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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们提出了焦虑在 SIB 的发生和维持中的作用。 为了检验这一假设，我们研究了八只成年雄性恒河猴（四只 SIB；四只对照）对不同剂量的致焦虑苯二氮卓 (BDZ) 反向激动剂 FG 7142（媒介物，0.1、0.3、1.0 mg/kg， IM）以混合受试者内设计给出。 所有动物的治疗间隔为 3 周。 治疗后 15 分钟收集行为数据，持续一小时，然后立即采血，分别通过酶免疫测定法和放射免疫测定法进行血浆皮质醇和 ACTH 分析。 最高剂量的 FG 7142 循环皮质醇浓度显着增加（F = 2.98，p 小于 0.05）。 令人惊讶的是，与对照组相比，SIB 猴中皮质醇水平较高也产生了总体影响（F = 11.45，p 小于 0.005）。 ACTH 值不会因剂量或组别而显着变化。 尽管据报道 FG 7142 在本研究中使用的剂量下会在恒河猴中产生焦虑行为（例如，抓挠增加），但我们发现在组间或组间给药没有可靠的行为影响。 总之，我们的结果没有发现 SIB 和对照猴之间 BDZ 受体功能存在差异的证据，这些差异会表现为对 FG 7142 攻击的不同反应。 这些发现并不排除 SIB 猴可能通过其他行为或生理测量表现出焦虑增加的可能性。