Effects of cholinergic agents on locomotor activity of P and NP rats.
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 micrograms/0.5 microliters), 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 micrograms/0.5 microliters), 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 80 micrograms/0.5 microliters), 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 micrograms/0.5 microliters) dose-dependently decreased LMA in both P and NP rats (to a maximum of approximately 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.
Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, USA.
S N
SN
Katner
W J
WJ
McBride
L
L
Lumeng
T K
TK
Li
J M
JM
Murphy
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D018678:Cholinergic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D008464:Mecamylamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology
D018678:Cholinergic Agents; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D010890:Pirenzepine; D008464:Mecamylamine; D012601:Scopolamine