Inhibitory influence of mecamylamine on ethanol withdrawal-induced symptoms in C57BL/6J mice.
Several reports show the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the behavioral effects of ethanol, including ethanol drinking and relapse. Therefore, this study evaluated the effects of mecamylamine, a nAChR antagonist, on ethanol withdrawal signs. Ethanol dependence was induced in C57BL/6J mice by ethanol liquid diet administration. Animals were provided with nutritionally balanced control liquid diet (600 kcal/l) as their sole nutrient source on day 0; from days 1 to 4, 3% v/v of ethanol, followed by 6% v/v of ethanol (from days 5 to 7), and 10% v/v of ethanol (from days 8 to 10) were incorporated into the liquid diet. On day 11, ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced physical signs were recorded. Results showed that acute administration of mecamylamine (1-4 mg/kg, intraperitoneally) dose-dependently attenuated ethanol withdrawal-induced signs, and these effects were comparable with those of diazepam (1-2 mg/kg, intraperitoneally). In addition, chronic administration of mecamylamine into ethanol diet-fed mice markedly attenuated the ethanol withdrawal sign scores, thus supporting the contention that nAChR is involved in ethanol dependence. In conclusion, our results suggest that mecamylamine exhibited inhibitory effects on ethanol withdrawal signs which could be mediated through nAChR.
Bhutada
Pravinkumar Satyanarayan
PS
Department of Pharmacology, Agnihotri College of Pharmacy, Pharmacology Division, Bapuji Wadi, Sindhi (Meghe), Wardha, India. psbhutada@live.com
Mundhada
Yogita R
YR
Bansod
Kuldeep U
KU
Umathe
Sudhir N
SN
Kahale
Vivek P
VP
Dixit
Pankaj V
PV
Mundhada
Dharmendra R
DR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D008297:Male; D008464:Mecamylamine / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D011978:Receptors, Nicotinic; D000431:Ethanol; D008464:Mecamylamine; D003975:Diazepam