title: The calcium channel antagonist, nimodipine, decreases operant self-administration of low concentrations of ethanol.
abstract: This study examined effects of the dihydropyridine calcium channel antagonist, nimodipine, on operant self-administration of ethanol, under a progressive-ratio schedule of reinforcement, by hooded Lister rats. Calcium channel antagonists have been reported to decrease the ethanol withdrawal syndrome, the development of tolerance to ethanol and ethanol consumption; and dihydropyridine binding site density in the central nervous system (CNS) is increased by chronic alcohol treatment. In addition, these drugs decrease reinforcing effects of psychostimulants. In the present studies, nimodipine was administered, once weekly, at either 10 or 50 mg/kg intraperitoneally (i.p.). At 10 mg/kg, nimodipine decreased the break point, and number of reinforcers obtained, for ethanol concentrations of 5, 10 and 15%. At 50mg/kg, nimodipine only decreased the break point, and number of reinforcers, for 5% ethanol. Responding for higher concentrations of ethanol was unaffected by nimodipine, as was responding when ethanol was replaced by water. The break point for 10% sucrose, but not for 1% or 0.1%, was decreased by 50 mg/kg nimodipine, but 10 mg/kg nimodipine had no effect on sucrose-reinforced responding. The 50 mg/kg dose of nimodipine decreased motor activity, but 10 mg/kg nimodipine only slightly decreased static activity counts. The results suggest that nimodipine, at the lower dose tested, decreased the reinforcing properties of low concentrations of ethanol.
authors.affiliation: Department of Psychology, Science Laboratories, Durham, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Smith
authors.forename: W P
authors.initials: WP
authors.lastname: Watson
authors.forename: D N
authors.initials: DN
authors.lastname: Stephens
authors.forename: H J
authors.initials: HJ
authors.lastname: Little
mesh_terms: D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003864:Depression, Chemical; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration; D013395:Sucrose / Q000494:pharmacology
chemical_list: D000427:Alcohol Deterrents; D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D000431:Ethanol; D013395:Sucrose; D009553:Nimodipine