Central behavioral interactions between ethanol, (-)-nicotine, and (-)-cotinine in mice.
A high correlation between alcohol use and smoking has long been suggested by epidemiological data. We examined the potential behavioral interactions between ethanol and nicotine using ethanol-induced motor incoordination as the test response in mice. Effect of pretreatment of various doses of (-)-nicotine, (-)-cotinine, a major metabolite of nicotine, and (+)-nicotine administered ICV on ethanol (IP)-induced motor incoordination was investigated. (-)-Nicotine (0.19, 0.38, 0.77 and, 1.54 nmoles ICV) produced significant attenuation of motor incoordination due to ethanol (2 g/kg IP) in a nearly dose-related manner which was blocked by ICV hexamethonium and trimethaphan, both purported nicotinic antagonists. (-)-Cotinine (0.35, 0.70, 1.41 nmole ICV) produced similar attenuation but was les potent than (-)-nicotine. Attenuation by (+)-nicotine (0.19, 0.38, and 0.77 nmoles ICV) was also significant but only at 0.77 nmole dose level. (+)-Nicotine-induced attenuation of motor incoordination by ethanol was antagonized by nicotinic antagonists. Data obtained suggest a central behavioral interaction between ethanol and nicotine at least through the participation of cholinergic nicotinic receptors.
Dar
M S
MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Li
C
C
Bowman
E R
ER
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003367:Cotinine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors; D014294:Trimethaphan / Q000008:administration & dosage / Q000494:pharmacology
D000431:Ethanol; D014294:Trimethaphan; D009538:Nicotine; D003367:Cotinine