Calcium channel antagonists attenuate cross-sensitization to the rewarding and/or locomotor effects of nicotine, morphine and MK-801.
The present study focused on the evaluation of behavioural cross-sensitization, particularly in locomotor activities and conditioned rewarding effects, between nicotine and morphine, cocaine, amphetamine or MK-801. Nicotine (0.5 mg kg(-1))-experienced mice manifested an enhanced locomotor response to morphine (5 mg kg(-1)) or MK-801 (0.3 mg kg(-1)). No cross-sensitization was observed between nicotine and amphetamine (2 mg kg(-1)) or cocaine (15 mg kg(-1)). Additionally, the L-type voltage-dependent calcium-channel antagonists, nimodipine and verapamil, but not diltiazem, at a dose of 20 mg kg(-1) injected before morphine or MK-801 challenge, blocked the expression of this cross-sensitization. In the second test, an enhancement of morphine place conditioning in rats pre-exposed to nicotine (0.5 mg kg(-1), injected daily for 5 days) was demonstrated. After two conditioning sessions, morphine (5 mg kg(-1)) induced a clear place preference only in animals that had previously received nicotine injections. The administration of nimodipine (10 and 20 mg kg(-1)), verapamil (10 and 20 mg kg(-1)) and diltiazem (10 and 20 mg kg(-1)) prior to nicotine dose-dependently prevented this sensitization to the rewarding effect of morphine produced by prior injections of nicotine. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in the appetitive effects of nicotine and morphine and in the sensitized locomotor stimulant effects of nicotine and morphine or MK-801.
Department of Pharmacodynamics, Skubiszewski Medical University of Lublin, Staszica 4, 20-081, Poland. gragab@panaceum.am.lublin.pl
Grazyna
G
Biala
Barbara
B
Weglinska
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003216:Conditioning, Operant; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004347:Drug Interactions; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
D002121:Calcium Channel Blockers; D005731:Ganglionic Stimulants; D009294:Narcotics; D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate; D009538:Nicotine; D009020:Morphine