α-Subunit G-protein antisense oligodeoxynucleotide effects on supraspinal ( i.c.v.) α 2-adrenoceptor antinociception in mice

Abstract

An in vivo antisense strategy was used to examine the involvement of G-protein subunits in supraspinal (intracerebroventricular; i.c.v.) α 2-adrenoceptor-mediated antinociception. Mice that were injected with 33-mer antisense oligodeoxyribonucleotides (6 nmol) or vehicle were tested (tailflick) with an agonist (clonidine, guanfacine or BH-T 920) administered i.c.v. 18–24 h later. G i3α antisense treatment attenuated BH-T 920 and clonidine-induced antinociception. G i2α antisense produced differential effects on the three agonists. G i1α and G s α antisense treatment had no significant effect. Together with the previous demonstration that i.c.v. μ-opioid antinociception is mediated via G i2α, the present results suggest that different receptors may mediate antinociception via different G-protein subunits and, hence, that specific subunits might offer novel targets for drug discovery.