Effects of Cholinergic Agents on Locomotor Activity of P and NP Rats

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Abstract
Experiments were undertaken to compare the selectively bred, alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rat lines for differences in the locomotor activity (LMA) response to intracerebroventricular infusions of muscarinic‐ and nicotinic‐cholinergic agents. Scopolamine, a nonselective muscarinic antagonist (40 to 120 μg/0.5 μl), dose‐dependently increased LMA in both P and NP rats (up to 90 to 100% above baseline; p < 0.05). On the other hand, pirenzepine, a selective M1 muscarinic antagonist (10 to 80 μg/0.5 μl), decreased LMA in P and NP rats (as much as 35 to 40% below control values; p < 0.05). Mecamylamine, a nicotinic antagonist (20 to 120 μg/0.5 μl), also decreased LMA in P and NP rats (as much as 30 to 40% below baseline; p < 0.05). The agonist nicotine (20 to 80 μg/0.5 μl) dose‐dependently decreased LMA in both P and NP rats (to a maximum of ˜60 to 65% below control values; p < 0.05). Based on standardized z‐scores, NP rats were more sensitive (p < 0.05) to the locomotor depressant effects of nicotine than P rats, whereas no differences were observed for standardized z‐scores between the P and NP lines on the effects of scopolamine, pirenzepine, or mecamylamine on LMA. The results suggest that subtypes of muscarinic and nicotinic receptors are involved in regulating LMA in a complex manner, with the M1 subtype possibly mediating behavioral activation, and that P and NP rats may possess innate differences in CNS nicotinic receptors regulating LMA.

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