INVOLVEMENT OF CNS CHOLINERGIC SYSTEMS IN ALCOHOL-DRINKING OF P-RATS

Experiments were undertaken to determine if CNS muscarinic- and nicoti nic-cholinergic receptors are involved in regulating alcohol drinking of rats from the selectively-bred alcohol-preferring P line. Intracere broventricular (i.c.v.) drug infusions were administered into the late ral ventricle of female P rats 15 minutes before ethanol access. The m uscarinic antagonists pirenzepine and scopolamine were tested on limit ed access (4 hours/day to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Nicotine and the nicotinic antagonist meca mylamine were rested on limited access (4 hours/day) to 10% (v/v) etha nol and 0.0125% saccharin solutions. Food was available ad libitum and water was available during the remaining 20 hours. The baseline ethan ol intakes ranged between an average of 3.0 +/- 0.3 g/kg/4 hours and 3 .4 +/- 0.3 g/kg /4 hours. Administration of 40-100 mu g pirenzepine (M -1-selective antagonist) had no effect on ethanol, food or water consu mption. However, 20-80 mu g scopolamine, a non-selective muscarinic an tagonist, dose-dependently decreased ethanol intake as much as 60% (p < 0.05) without altering food or water consumption. The nicotinic anta gonist mecamylamine (20-120 mu g) did not alter ethanol intake, but ni cotine (40-80 mu g) dose-dependently decreased ethanol drinking as muc h as 60% within the first 30 minutes (p < 0.05) without an effect on s accharin intake. The results suggest that: (a), muscarinic receptors, with the possible exception of the M-1 subtype, are involved in regula ting alcohol drinking and (b), activation of nicotinic receptors can r educe alcohol drinking of the P line of rats.