Congenital Kir6.2 deficiency, but not acute KATP channel blockade, attenuates apomorphine-induced locomotor activity in mice.

Kir6.2, a pore-forming subunit of adenosine triphosphate-sensitive potassium (KATP) channels, is expressed in dopaminergic neurons, which play critical roles in motor regulation and psychiatric disorders. Although Kir6.2 deficiency has been associated with altered emotional behavior, its functional contribution to dopaminergic responsiveness remains incompletely understood. In the present study, we investigated the role of Kir6.2 in dopamine receptor-dependent behavioral regulation using complementary genetic and acute pharmacological approaches. Administration of the dopamine receptor agonist apomorphine robustly increased spontaneous locomotor activity in wild-type mice of both sexes; this response was significantly attenuated in Kir6.2-/- mice, as evidenced by a reduced peak response and decreased locomotor activity during the 30-60 min post-injection period. Baseline locomotor activity prior to apomorphine administration did not differ between genotypes, indicating preserved spontaneous motor function. In contrast, acute KATP channel blockade with glibenclamide failed to reproduce the Kir6.2-deficient phenotype under the present experimental conditions, and the pharmacological findings should therefore be interpreted as inconclusive with respect to central KATP channel function. The sucrose preference test was unchanged in Kir6.2-/- mice, suggesting intact basal hedonic processing. Moreover, dopamine-related protein expression in the nucleus accumbens (NAcc) following apomorphine administration revealed no detectable genotype differences. Collectively, these findings demonstrate that congenital Kir6.2 deficiency preferentially impairs dopamine receptor-dependent motor activation without affecting basal hedonic behavior and suggest that the observed behavioral alterations may reflect, at least in part, long-term or developmental adaptations in dopaminergic neural circuits.