Short K R, Maier S F
Department of Psychology, University of Colorado, Boulder 80309.
Pharmacol Biochem Behav. 1993 Aug;45(4):827-35. doi: 10.1016/0091-3057(93)90128-g.
Effects of benzodiazepine receptor-active compounds on inescapable shock-produced changes in social interaction were studied in the rat. Inescapably shocked animals exhibited less social interaction in a novel situation than did escapably shocked or unshocked rats 24 h after shock. Administration of the selective benzodiazepine receptor antagonist flumazenil at the time of shock prevented the decrease in social interaction. Social interaction was unaffected by the same treatment at the time of measurement. Reduction in social interaction induced by inescapable stress endured for 48-72 h following stressor exposure but was absent 168 h after stress. It was subject to antagonist blockade at all measured time points. Stress-induced decreases in social interaction were also blocked by the benzodiazepine chlordiazepoxide given at the time of shock treatment. The receptor antagonist did not reverse this blockade. An inverse agonist, the beta-carboline FG 7142, administered in place of inescapable shock, produced an identical pattern of social interaction in a dose-dependent manner. The inverse agonist effect was also reversed by the antagonist. The results from antagonist, agonist, and inverse agonist treatments all suggest that an endogenous benzodiazepine receptor inverse agonist is released at the time of inescapable shock and is involved in producing the changes in social interaction subsequently measured.
研究了苯二氮䓬受体活性化合物对大鼠不可逃避电击所致社会行为变化的影响。不可逃避电击的动物在电击24小时后的新环境中表现出的社会行为比可逃避电击或未电击的大鼠少。电击时给予选择性苯二氮䓬受体拮抗剂氟马西尼可防止社会行为减少。测量时相同处理对社会行为无影响。不可逃避应激诱导的社会行为减少在应激源暴露后持续48 - 72小时，但在应激168小时后不存在。在所有测量时间点均受拮抗剂阻断。电击治疗时给予苯二氮䓬类药物氯氮䓬也可阻断应激诱导的社会行为减少。受体拮抗剂不能逆转这种阻断作用。一种反向激动剂β-咔啉FG 7142，代替不可逃避电击给药，以剂量依赖方式产生相同的社会行为模式。拮抗剂也可逆转反向激动剂的作用。拮抗剂、激动剂和反向激动剂治疗的结果均表明，不可逃避电击时释放内源性苯二氮䓬受体反向激动剂，且其参与随后测量的社会行为变化的产生。
