Antagonism of scopolamine-induced memory impairments in rats by the muscarinic agonist RU 35,926 (CI-979)

The promnesic effects of RU 35,926 (CI-979), a muscarinic receptor agonist, were evaluated on memory impairments induced by the muscarinic antagonist scopolamine, using a radial arm maze task, in comparison with tetrahydroaminoacridine (THA), a cholinesterase inhibitor. Groups of rats were trained in a standard version of the radial maze until they had attained an asymptotic level of performance. The animals were then retested with one trial a day. Twenty minutes before each retest, the rats were given subcutaneous administration of 0.1 mg/kg scopolamine. Oral administration of RU 35,926 (0.02, 0.05, 0.1, 0.2, and 0.5 mg/kg) 30 min before memory retest markedly reduced or suppressed the scopolamine-induced deficit. This reduction was evidenced by a significant decrease in the different types of errors and an increase in the number of correct responses. THA (3 mg/kg, intraperitoneally or orally) given 20 min to testing also significantly reduced or suppressed the scopolamine-induced deficits. These results show that RU 35,926 possesses the capacity to reduce memory impairments induced by a deficit of cholinergic transmission in the rat.