Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Abstract

Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetamine-treated mice. The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.