Intracellular calcium chelation with BAPTA-AM modulates ethanol-induced behavioral effects in mice.
Calcium (Ca(2+)) has been characterized as one of the most ubiquitous, universal and versatile intracellular signaling molecules responsible for controlling numerous cellular processes. Ethanol-induced effects on Ca(2+) distribution and flux have been widely studied in vitro, showing that acute ethanol administration can modulate intracellular Ca(2+) concentrations in a dose dependent manner. In vivo, the relationship between Ca(2+) manipulation and the corresponding ethanol-induced behavioral effects have focused on Ca(2+) flux through voltage-gated Ca(2+) channels. The present study investigated the role of inward Ca(2+) currents in ethanol-induced psychomotor effects (stimulation and sedation) and ethanol intake. We studied the effects of the fast Ca(2+) chelator, BAPTA-AM, on ethanol-induced locomotor activity and the sedative effects of ethanol. Swiss (RjOrl) mice were pretreated with BAPTA-AM (0-10 mg/kg) 30 min before an ethanol (0-4 g/kg) challenge. Our results revealed that pretreatment with BAPTA-AM prevented locomotor stimulation produced by ethanol without altering basal locomotion. In contrast, BAPTA-AM reversed ethanol-induced hypnotic effects. In a second set of experiments, we investigated the effects of intracellular Ca(2+) chelation on ethanol intake. Following a drinking-in-the-dark methodology, male C57BL/6J mice were offered 20% v/v ethanol, tap water, or 0.1% sweetened water. The results of these experiments revealed that BAPTA-AM pretreatment (0-5 mg/kg) reduced ethanol consumption in a dose-dependent manner while leaving water and sweetened water intake unaffected. Our findings support the role of inward Ca(2+) currents in mediating different behavioral responses induced by ethanol. Our results are discussed together with data indicating that ethanol appears to be more sensitive to intracellular Ca(2+) manipulations than other psychoactive drugs.
Área de Psicobiología, Universtitat Jaume I, Avda. Sos Baynat s/n, 12071, Castellón, Spain.
Pablo
P
Baliño
Lidón
L
Monferrer
Raúl
R
Pastor
Carlos M G
CM
Aragon
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*
D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D000431:Ethanol; D004533:Egtazic Acid