Herzog C D, Stackman R W, Walsh T J
Department of Psychology, Rutgers University, New Brunswick, New Jersey 08903, USA.
Neurobiol Learn Mem. 1996 Nov;66(3):341-52. doi: 10.1006/nlme.1996.0074.
GABAA/benzodiazepine receptors in the medial septum modulate the activity of cholinergic neurons that innervate the hippocampus. Injection of benzodiazepine (BDZ) agonists into the medial septum impairs working memory performance and decreases high-affinity choline transport (HAChT) in the hippocampus. In contrast, intraseptal injection of the BDZ antagonist flumazenil increases HAChT and prevents the memory deficits induced by systemic BDZs. The present studies attempted to further characterize the behavioral effects of medial septal injections of flumazenil to an endogenous negative modulator of the GABAA/BDZ receptor complex, diazepam binding inhibitor (DBI). Male Sprague-Dawley rats were cannulated to study the effects of intraseptal injections of these BDZ ligands on spatial working memory, anxiety-related behaviors in the elevated plus maze, and on general locomotor activity. Intraseptal flumazenil (10 nmol/0.5 microliter) produced a delay-dependent enhancement of DNMTS performance after an 8-h, but not a 4-h, delay interval. This promnestic dose of flumazenil had no effect on locomotor activity and did not produce changes in measures of anxiety on the plus maze. Intraseptal injection of DBI had no effect (8 nmol/0.5 microliter) or slightly impaired (4 nmol/0.5 microliter) DNMTS radial maze performance following an 8-h delay, without producing changes in locomotion or plus maze behavior. These data demonstrate that flumazenil has a unique profile of activity in enhancing working memory following intraseptal injection.
内侧隔区的GABAA/苯二氮䓬受体调节支配海马体的胆碱能神经元的活性。向内侧隔区注射苯二氮䓬（BDZ）激动剂会损害工作记忆表现，并降低海马体中的高亲和力胆碱转运（HAChT）。相比之下，向隔区内注射BDZ拮抗剂氟马西尼可增加HAChT，并预防全身性BDZs诱导的记忆缺陷。本研究试图进一步表征向内侧隔区注射氟马西尼对GABAA/BDZ受体复合物的内源性负调节剂——地西泮结合抑制剂（DBI）的行为影响。将雄性Sprague-Dawley大鼠插管，以研究向隔区内注射这些BDZ配体对空间工作记忆、高架十字迷宫中与焦虑相关的行为以及一般运动活动的影响。隔区内注射氟马西尼（10 nmol/0.5微升）在延迟8小时而非4小时后，对延迟非匹配样本（DNMTS）表现产生了延迟依赖性增强。这个具有记忆增强作用剂量的氟马西尼对运动活动没有影响，也没有使十字迷宫中的焦虑测量指标发生变化。隔区内注射DBI（8 nmol/0.5微升）对DNMTS放射状迷宫表现没有影响，或在延迟8小时后轻微损害了（4 nmol/0.5微升）DNMTS放射状迷宫表现，且没有使运动或十字迷宫行为发生变化。这些数据表明，氟马西尼在隔区内注射后增强工作记忆方面具有独特的活性特征。
