The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

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Abstract
1 The effects of the dihydropyridine calcium channel blocker nifedipine and the activator Bay K 8644 were investigated in different behavioural tests involving dopaminergic systems. These were the discriminative stimulus induced by amphetamine, rotational behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions and apomorphine-induced yawning in rats. 2 The yawning induced by apomorphine (40 μg kg−1 s.c.) was significantly potentiated by nifedipine (5–10 mg kg−1 i.p.). Bay K 8644 (0.05-0.5 mg kg−1 i.p.) dose-dependently inhibited yawning induced by apomorphine (80 μg kg−1 s.c.) and, at 0.4 mg kg−1, inhibited the nifedipine potentiation of apomorphine-induced yawning. In contrast to their effects on apomorphine-induced yawning, nifedipine and Bay K 8644 had no effect on apomorphine-induced penile erection. 3 Bay K 8644 (0.06-0.5 mg kg−1 i.p.) and nifedipine (5–20 mg kg−1 i.p.) had no dose-related effect on the discrimination performance of rats trained to discriminate amphetamine from saline. However, nifedipine dose-dependently reduced the response rate of amphetamine-treated rats. Bay K 8644 had no effect on this measure except at high doses that also caused disruption. 4 Neither nifedipine (5–10 mg kg−1 i.p.) nor Bay K 8644 (0.06-0.5 mg kg−1 i.p.) affected the turning behaviour induced by amphetamine (1 mg kg−1 i.p.) in rats with unilateral 6-OHDA lesion of the medial forebrain bundle, and did not induce turning themselves. 5 As the dihydropyridine compounds affected apomorphine-induced yawning but not penile erection, and did not affect amphetamine-induced rotation or drug discrimination, it seems unlikely that they are affecting dopamine release in vivo.