Tacrolimus, a specific inhibitor of calcineurin, modifies the locomotor activity of quinpirole, but not that of SKF82958, in male rats

In the present study, we examined the effect of tacrolimus, a specific inhibitor of calcineurin, on the locomotor activity elicited by the selective dopamine D(1) receptor agonist (+/-) 6-chloro-7,8-dyhydroxy-3allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine (SKF82958) and the dopamine D(2)/D(3) receptor agonist quinpirole, in male Wistar rats. Tacrolimus (0.5, 1, 2 or 5 mg/kg, i.p.) alone had no significant effect on basal locomotor activity. The dose-related increase in locomotor activity produced by the administration of SKF82958 (0.1, 1 or 5 mg/kg, i.p.) was not significantly altered by 2 mg/kg of tacrolimus. In addition, the increase in locomotor activity produced by 1 mg/kg of SKF82958 was not significantly altered by tacrolimus (0.5, 1, 2 or 5 mg/kg, i.p.). The administration of quinpirole (0.1, 0.25, 0.5, 1 or 3 mg/kg, i.p.) produced a biphasic response, with the minimum and maximal increase in locomotor activity occurring at 0.1 and 1 mg/kg, respectively. The pretreatment of 2 mg/kg of tacrolimus, compared to vehicle-treated animals, significantly lowered the dose of quinpirole that produce a maximal effect on locomotor activity from 1 to 0.5 mg/kg but did not significantly alter the minimum response. The increase in locomotor activity produced by 0.5 mg/kg of quinpirole was significantly potentiated by 0.5, 1, 2 or 5 mg/kg of tacrolimus compared to vehicle-treated animals. Our results suggest that calcineurin may play a role in the alteration of locomotor activity produced by dopamine D(2)/D(3) receptors, but not dopamine D(1) receptors.