Pharmacology Biochemistry & Behavior, Vol. 33, pp. 919-922. e Pergamon Press plc, 1989. Printed in the U.S.A. 0091-3057/89 $3.00 + .00 BRIEF COMMUNICATION Reversal of a Mecamylamine-Induced Cognitive Deficit With the DE Agonist, LY 171555 EDWARD D. LEVIN, .1 SUSAN R. McGURK,I" JED E. ROSE* AND LARRY L. BUTCHERt *Nicotine Research Lab, VA Medical Center, Durham, NC 27705 f'Department of Psychology, University of California, Los Angeles, CA 90024-1563 Received 27 February 1989 LEVIN, E. D., S. R. McGURK, J. E. ROSE AND L. L. BUTCHER. Reversalofa mecamylamine-induced cognitive deficit with the D 2 agonist, L Y 171555. PHARMACOL BIOCHEM B EHAV 33(4) 919-922, 1989.--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 impariment. 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~ antagonist SCH 23390 but is unaffected by the D2 antagonist raclopride. In contrast, the cognitive impairment caused by the nicotinic antagonist mecamylamine is unaffected by SCH 23390 but is potentiated by raclopride. In the current study, the De agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecarnylamine. In contrast, the D~ agonist SKF 38393 was not found to be effective. Thus, we have found selective dopaminergic D~ and De treatments which counteract the adverse cognitive effects of either nicotinic or muscarinic blockade. A combination of these treatments may be useful in treating the cognitive effects of generalized eholinergic underactivation. Radial-arm maze Nicotinic Dopaminergic D 1 De SKF 38393 LY 171555 Mecamylamine Agonist Antagonist IN previous studies, we found that scopolamine-induced deficits in radial-arm maze choice accuracy could be reversed by dopamine (DA) receptor blockade (10,15). This reversal could also be seen after selective blockade of D~ dopaminergic receptors (10). Selective D 2 blockade was ineffective. It seems that in cognitive as well as motor function there is a reciprocal interaction of DA and muscarinic acetylcholine (ACh) systems. Recently, it has also been shown that as with muscarinic ACh receptors, blockade of nicotinic ACh receptors impairs radial-arm maze choice accuracy performance (11). Furthermore, nicotinic and muscarinic blockade act together in an additive fashion in disrupting choice accuracy in the radial-arm maze (13). Despite this additive effect, however, muscarinic blockade and nicotinic blockade have quite different interactions with DA receptor antagonists. In contrast to the haloperidol-induced reversal of the scopolamine effect, haloperi- dol potentiates the adverse effect that mecamylamine has on radial-arm maze choice accuracy (16). This potentiation seems to be mediated via a different DA receptor subtype. Whereas D~, but not D2, receptor blockade reverses the choice accuracy deficit resulting from muscarinic antagonism, D2, but not D1, receptor blockade potentiates choice accuracy deficit resulting from nico- tinic blockade (17). The present study was conducted to determine whether or not the mecarnylamine-induced choice accuracy deficit in the radial-arm maze could be reversed by a selective D 2 agonist. METHOD Subjects The ten female Sprague-Dawley rats (Bantin & Kingman Inc., Fremont, CA) used in the present experiment were housed singly in the test room on a reverse 12:12-hr light:dark cycle (lights came on at 1800). All behavioral testing was conducted during the dark phase in a dimly-lit room. The rats had ad lib access to drinking water but were maintained on a restricted feeding to keep their ~Requests for reprints should be addressed to Dr. Edward Levin, Nicotine Research Laboratory 151, VA Medical Center, 508 Fulton St., Durham, NC 27095. 919