EFFECTS OF CHOLINERGIC AGENTS ON LOCOMOTOR-ACTIVITY OF P-RATS AND NP-RATS

Experiments were undertaken to compare the selectively bred, alcohol-p referring (P) and alcohol-nonpreferring (NP) rat lines for differences in the locomotor activity (LMA) response to intracerebroventricular i nfusions of muscarinic- and nicotinic-cholinergic agents. Scopolamine, a nonselective muscarinic antagonist (40 to 120 mu g/0.5 mu l), dose- dependently increased LMA in both P and NP rats (up to 90 to 100% abov e baseline; p < 0.05), On the other hand, pirenzepine, a selective M(1 ) muscarinic antagonist (10 to 80 mu g/0.5 mu l), decreased LMA in P a nd NP rats (as much as 35 to 40% below control values; p < 0.05). Meca mylamine, a nicotinic antagonist (20 to 120 mu g/0.5 mu l), also decre ased LMA in P and NP rats (as much as 30 to 40% below baseline; p < 0. 05). The agonist nicotine (20 to 80 mu g/0.5 mu l) dose-dependently de creased LMA in both P and NP rats (to a maximum of similar to 60 to 65 % below control values; p<0.05). Based on standardized z-scores, WP ra ts were more sensitive (p < 0.05) to the locomotor depressant effects of nicotine than P rats, whereas no differences were observed for stan dardized z-scores between the P and NP lines on the effects of scopola mine, pirenzepine, or mecamylamine on LMA. The results suggest that su btypes of muscarinic and nicotinic receptors are involved in regulatin g LMA in a complex manner, with the M(1) subtype possibly mediating be havioral activation, and that P and NP rats may possess innate differe nces in CNS nicotinic receptors regulating LMA.