Reversal of a mecamylamine-induced cognitive deficit with the D 2 agonist, LY 171555

Abstract

Pharmacological blockade of either nicotinic or muscarinic cholinergic receptors has been found to impair choice accuracy in the radial-arm maze. Simultaneous blockade of both of these receptor types causes an additive impairment. However, despite these common effects, nicotinic and muscarinic receptors have been found to have differential involvement with dopamine receptors. The cognitive impairment caused by the muscarinic antagonist scopolamine is reversed by the D 1 antagonist SCH 23390 but is unaffected by the D 2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is is potentiated by raclopride. In the current study, the D 2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine. In contrast, the D 1 agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D 1 and D 2 treatments which counteract the adverse cognitive effects of their nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized cholinergic underactivation.