Involvement of alpha 6 nicotinic receptor subunit in nicotine-elicited locomotion, demonstrated by in vivo antisense oligonucleotide infusion

ENHANCED locomotion in a habituated environment is a well documented effect of nicotine mediated by the mesotelencephalic dopaminergic system. The nicotinic receptor subunit alpha 6 is, among other subunits, strongly expressed in the dopaminergic neurons of the mesencephalon. To examine the functional role of this subunit, we inhibited its expression in vivo using antisense oligonucleotides. lit vitro treatments of embryonic mesencephalic neuron cultures demonstrated that the alpha 6 antisense oligonucleotides caused a marked decrease in the level of alpha 6 subunit protein. In vivo, 1 week infusion of alpha 6 antisense oligonucleotides by osmotic mini-pump reduced the effect of nicotine on locomotor activity in habituated environment by 70%. These data support the notion that the effects of nicotine on the dopaminergic system involve alpha 6 subunit containing nAChRs.