Intracellular calcium chelation with BAPTA-AM modulates ethanol-induced behavioral effects in mice

Abstract

Calcium (Ca2+) 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 Ca2+ distribution and flux have been widely studied in vitro, showing that acute ethanol administration can modulate intracellular Ca2+ concentrations in a dose dependent manner. In vivo, the relationship between Ca2+ manipulation and the corresponding ethanol-induced behavioral effects have focused on Ca2+ flux through voltage-gated Ca2+ channels. The present study investigated the role of inward Ca2+ currents in ethanol-induced psychomotor effects (stimulation and sedation) and ethanol intake. We studied the effects of the fast Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ manipulations than other psychoactive drugs.