Tacrolimus, a specific inhibitor of calcineurin, modifies the locomotor activity of quinpirole, but not that of SKF82958, in male rats.
European Journal of Pharmacology(2002)
摘要
In the present study, we examined the effect of tacrolimus, a specific inhibitor of calcineurin, on the locomotor activity elicited by the selective dopamine D1 receptor agonist (±) 6-chloro-7,8-dyhydroxy-3allyl-1-phenyl-2,3,4,5-tetra-hydro-1H-benzazepine (SKF82958) and the dopamine D2/D3 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 D2/D3 receptors, but not dopamine D1 receptors.
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关键词
Tacrolimus,Calcineurin,Dopamine D1 receptor,Dopamine D2 receptor,Dopamine D3 receptor,Locomotor activity
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