Effect of post-training injections of flumazenil into the amygdala, hippocampus and septum on retention of habituation and of inhibitory avoidance in rats

Adult rats were submitted to two different behavioral tasks using the same apparantus: the habituation of exploration of the apparatus considered as a novel environment as measured by the decrease in number of reaings and of ambulation between training and testing, and step-down inhibitory avoidance as measured by the increase in the latency to step down from a start platform into an electrified grid between the training and the test session.The training-test interval for both tasks was 20 h.The immediate post-training injection of the benzodiazepine receptor antagonist flumazenil (10 nmol) bilateral into the hippocampus enhanced retention of the two tasks.Application of the same drug, at the same dose to the septum or amygdala had no effect on habituation but enhanced retention of the avoidance task. The data are consistent with previous findings showing that both tasks are accompanied by the release of benzodiazepine like immunoreactivity in the three structures and that this release is greater after the avoidance task. The present findings suggest a differential regional involvement of endogenous benzodiazepine-mediated mechanisms in memory modulation, according to the task undertaken

Biochemical and behavioral effects of intraseptal microinjection of fasciculin, an irreversible acetylcholinesterase inhibitor

We examined the effect, in rats, of an intraseptal microinjection of fasciculin (FAS), an irreversible peptide acetylcholinesterase (AChE) inhibitor, on a)AChE activity measured in septum and hippocampus, b)3H-quinuclidiny benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepan (3H-FNZ) binding to hippocampal benzodiazepine receptors as a control for QNB and OXO binding, d) acquisition and retention in three different behavioral paradigms, i. e., water-finding (in which there is concomitant habituation to be apparatus), step-down inhibitory avoidance, and shuttle avoidance. AChE activity in septum decreased 2 days (-66%) and 5 days (-48%) after FAS microinjection; a slight reduction (-35%) occurred in the dorsal hippocampus on day 2 (P<0.05; N=6 per group); no changes in AChE activity were observed in ventral hippocampus ion day 2 or day 5. No changes in 3H-QNB, 3H-OXO, or 3H-FNZ binding constants were demonstrable in the hippocampus either 2 or 5 days after intraseptal FAS adminstration. No changes in training or test session performance in any of the three behavioral situations were observed 2-3 days after the intraseptal microinjection of FAS. The persistent inhibition of septal AChE caused by FAS microinjection into the septum is not sufficient to induce major changes either in hippocampal cholinergic muscarinic receptors, or in the learning or retention of behaviors regulated by the septum and/or hippocampus