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

1. 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-quinuclidinyl benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepam (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 the apparatus), step-down inhibitory avoidance, and shuttle avoidance. 2. 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 less than 0.05; N = 6 per group); no changes in AChE activity were observed in ventral hippocampus on day 2 or day 5. 3. 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 administration. 4. 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. 5. 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.