The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

• Published in: British journal of pharmacology 1989-12, Vol.98 (4), p.1312-1318
• Main Authors: Bourson, Anne, Gower, Alma J., Mir, Anis K., Moser, Paul C.
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Amphetamine - pharmacology; Animals; Apomorphine - pharmacology; Behavior, Animal - drug effects; Biological and medical sciences; Cardiovascular system; Dihydropyridines - pharmacology; Dopamine - physiology; Generalization (Psychology) - drug effects; Learning - drug effects; Male; Medial Forebrain Bundle - physiology; Medical sciences; Miscellaneous; Motor Activity - drug effects; Penile Erection - drug effects; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Sympathectomy, Chemical; Yawning - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1989.tb12679.x

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.