Involvement of CNS cholinergic systems in alcohol drinking of P rats

Experiments were undertaken to determine if CNS muscarinic- and nicotinic-cholinergic receptors are involved in regulating alcohol drinking of rats from the selectively-bred alcohol-preferring P line. Intracerebroventricular (i.c.v.) drug infusions were administered into the lateral ventricle of female P rats 15 minutes before ethanol access. The muscarinic antagonists pirenzepine and scopolamine were tested on limited access (4 hours/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Nicotine and the nicotinic antagonist mecamylamine were tested on limited access (4 hours/day) to 10% (v/v) ethanol and 0.0125% saccharin solutions. Food was available ad libitum and water was available during the remaining 20 hours. The baseline ethanol 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 m g pirenzepine (M1-selective antagonist) had no effect on ethanol, food or water consumption. However, 20-80 m g scopolamine, a non-selective muscarinic antagonist, dosedependently decreased ethanol intake as much as 60% (p < 0.05) without altering food or water consumption. The nicotinic antagonist mecamylamine (20-120 m g) did not alter ethanol intake, but nicotine (40-80 m g) dose-dependently decreased ethanol drinking as much as 60% within the first 30 minutes (p < 0.05) without an effect on saccharin intake. The results suggest that: (a), muscarinic receptors, with the possible exception of the M1 subtype, are involved in regulating alcohol drinking and (b), activation of nicotinic receptors can reduce alcohol drinking of the P line of rats.