Calcium channel antagonists suppress nicotine-induced place preference and locomotor sensitization in rodents.
The influence of calcium channel antagonists on the behavioral sensitization to nicotine-induced hyperlocomotion and place preference was investigated. Locomotor sensitization in mice was produced by injecting nicotine (0.5 mg/kg, i.p.) for 5 consecutive days before placement in an apparatus in which locomotor activity was evaluated for 1 h. One week later, activity of mice was recorded after challenge with the same dose of nicotine. The L-type voltage-dependent calcium channel antagonists: nimodipine (5, 10 and 20 mg/kg, i.p.), verapamil (5, 10 and 20 mg/kg, i.p.) and diltiazem (5, 10 and 20 mg/kg, i.p.) were injected 15 min before each injection of nicotine (induction of sensitization) or acutely 15 min before a challenge nicotine injection (expression of sensitization). It was shown that the calcium channel blockers attenuated both the induction and expression of nicotine-induced locomotor sensitization in a dose-dependent manner. In the place preference paradigm, nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.5 mg/kg, i.p., 4 drug sessions). Pretreatment with nimodipine (10 mg/kg, i.p.), verapamil (10 mg/kg, i.p.) and diltiazem (10 mg/kg, i.p.) blocked nicotine-induced place conditioning. These results suggest the common calcium-dependent mechanisms of nicotine-induced behavioral sensitization and place preference.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009553:Nimodipine; D009538:Nicotine; D014700:Verapamil; D004110:Diltiazem