In vivo effects of (-)-nicotine on ethanol-induced increase in glucose utilization in the mouse cerebellum.
The purpose of this study was to investigate the possible in vivo effects of (-)-nicotine, ethanol, and an adenosine agonist N6-cyclohexyladenosine (CHA) when injected individually as well as in various combinations on glucose utilization in the fresh cerebellar slices of mice. Mice received ICV (-)-nicotine or CHA followed 5 min later by a test dose of ethanol (2 g/kg; IP). Animals were killed 20 min postethanol treatment and fresh slices (300 microns) of cerebellum were incubated in a glucose medium in Warburg flasks using 14C-glucose as a tracer. Trapped 14CO2 was counted to estimate glucose utilization. Ethanol treatment markedly accentuated glucose utilization, whereas the pretreatment with (-)-nicotine (125 and 250 ng, ICV) resulted in a significant attenuation in the ethanol-induced increase in glucose utilization. However, ICV (-)-nicotine (125 ng) alone did not produce any change in the cerebellar glucose utilization. The attenuation of ethanol-induced increase in glucose utilization by (-)-nicotine was nearly totally blocked by ICV hexamethonium, a purported nicotinic antagonist, suggesting participation of cholinergic-nicotinic receptors. The (-)-nicotine pretreatment also significantly attenuated both the ICV CHA (25 ng)-induced increase in glucose utilization and the accentuation of ethanol-induced increase in glucose utilization by CHA. The antagonistic effect of (-)-nicotine on CHA- and ethanol-induced increase in glucose utilization indicating an interaction between (-)-nicotine and ethanol and between (-)-nicotine and adenosine may suggest involvement of postreceptor (nicotinic and adenosine) mechanisms including ionic channels.
Anwer
J
J
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Dar
M S
MS
D000241:Adenosine / Q000032:analysis* / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*
D018738:Hexamethonium; D000431:Ethanol; D009538:Nicotine; D005947:Glucose; D000241:Adenosine