title: Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists.
abstract: In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.
authors.affiliation: Department of Pharmacology, University of Göteborg, Sweden.
authors.forename: J A
authors.initials: JA
authors.lastname: Engel
authors.forename: C
authors.initials: C
authors.lastname: Fahlke
authors.forename: P
authors.initials: P
authors.lastname: Hulthe
authors.forename: E
authors.initials: E
authors.lastname: Hård
authors.forename: K
authors.initials: K
authors.lastname: Johannessen
authors.forename: B
authors.initials: B
authors.lastname: Snape
authors.forename: L
authors.initials: L
authors.lastname: Svensson
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D000431:Ethanol; D009543:Nifedipine; D004298:Dopamine