EFFECTS OF ANTICHOLINESTERASE DRUGS TACRINE AND E2020, THE 5-HT3 ANTAGONIST ONDANSETRON, AND THE H-3 ANTAGONIST THIOPERAMIDE, IN MODELS OF COGNITION AND CHOLINERGIC FUNCTION

This study presents a comparison between two inhibitors of acetylcholi nesterase, tacrine and E2020 (Donepezil), the 5-HT3 receptor antagonis t ondansetron, and the H-3 receptor antagonist thioperamide, in models of cholinergic function and cognition in male, Lister hooded rats, Th e cognitive tests used were an operant VI20 task, the delayed match to position task (short-term memory) and the 5-choice serial reaction ti me task (attention), Scopolamine (SCOP) (0.075 mg/kg s.c.) was utilise d in both the short-term memory and attention tasks to impair performa nce, Both tacrine (1-30 mg/kg) and E2020 (1-10 mg/kg) similarly produc ed overt cholinomimetic signs of likely central origin (hypothermia, t remor), although tacrine produced more profound peripheral cholinomime tic signs (miosis, secretory signs:) than E2020, Tacrine (30 mg/kg) an d E2020 (10 mg/kg) reduced the number of reinforcements gained in the VI20 schedule, Similarly, hath drugs attenuated the SCOP-impairment mo dels in the short-term memory and attention tasks (1-3 mg/kg), Ondanse tron (10 ng/kg-1 mg/kg) and thioperamide (0.210 mg/kg) failed to elici t overt cholinomimetic signs or influence the number of food reinforce ments gained in the VI20 schedule, Neither ondansetron nor thioperamid e attenuated the SCOP-induced impairment in either cognitive task, Fro m the present studies, both E2020 and tacrine showed a similar behavio ural profile in the models used, although E2020 was about three times more potent. Furthermore, E2020 but not tacrine appeared to show some discrimination in eliciting central and peripheral cholinomimetic sign s, The failure of ondansetron and thioperamide to reverse a SCOP-induc ed deficit in these models is discussed.