Participation of L-type calcium channels in ethanol-induced behavioral stimulation and motor incoordination: effects of diltiazem and verapamil.
Calcium flux through voltage gate calcium channels (VGCC) is involved in many neuronal processes such as membrane depolarization, gene expression, hormone secretion, and neurotransmitter release. Several studies have shown that either acute or chronic exposure to ethanol modifies calcium influx through high voltage activated channels. Of special relevance is the L-type VGCC. Pharmacological manipulation of L-type calcium channels affects ethanol intake, ethanol discrimination and manifestations of withdrawal syndrome. The present study investigates the role of L-type channels on the psychomotor effects (stimulation and sedation/ataxia) of ethanol by testing the effects of different L-type calcium channel blockers (CCB) on such behaviors. Mice were pretreated intraperitoneally with the CCB, diltiazem (0-40 mg/kg) or verapamil (0-30 mg/kg) 30 min before ethanol (0-3.5 g/kg). Locomotion was measured in an open field chamber for 20 min immediately after ethanol. The two CCB tested prevented locomotor stimulation, but not locomotor suppression produced by ethanol. Doses of the two CCB which reduced ethanol stimulation, did not alter spontaneous locomotion. The ataxic effects of ethanol (1.25 g/kg), measured with an accelerating rotarod task, were not affected by diltiazem (20mg/kg) or verapamil (15 mg/kg). In addition, our results indicated that ethanol is more sensitive to the antagonism of L-type calcium channels than other drugs with stimulant properties; doses of the two CCB that reduced ethanol stimulation did not reduce the psychomotor effects of amphetamine, caffeine or cocaine. In conclusion, these data provide further evidence of the important involvement of L-type calcium channels in the behavioral effects produced by ethanol.
Baliño
Pablo
P
Area de Psicobiología, Universtitat Jaume I, Avda. Sos Baynat s/n, 12071 Castellón, Spain.
Pastor
Raúl
R
Aragon
Carlos M G
CM
D000704:Analysis of Variance; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D045442:Rotarod Performance Test; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000431:Ethanol; D014700:Verapamil; D004110:Diltiazem; D003042:Cocaine