The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

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 pg kg-s.c.) was significantly potentiated by nifedipine (5-10mgkg-'i.p.). Bay K 8644 (0.05-0.5mgkg-'i.p.) dose-dependently inhibited yawning induced by apomorphine (80upgkg-'s.c.) and, at 0.4mgkg-', 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 (0.06-0.5mgkg-i p.) and nifedipine (5-20mgkg-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 (5-10mgkg-i.p.) nor Bay K 8644 (0.06-0.5 mgkg-' i.p.) affected the turning behaviour induced by amphetamine (1 mgkg' 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.

Effects of repeated-dose isradipine on the abuse liability of cocaine.

“…The VAS and ARCI measures of subjective effect and the MCQ behavioral measure of reinforcement are those laboratory measures most predictive of abuse potential; therefore, we conclude that isradipine does not reduce cocaine's reinforcing effects in humans. These results are in contrast to preclinical data showing isradipine-related reductions in cocaine reinforcement (Kuzmin, Zvartau, Gessa, Martellotta, & Fratta, 1992; Martellotta et al, 1994) and dopamine release (Bourson et al, 1989; Pani et al, 1990). Whereas this suggests possible limitations of preclinical animal models, there also are limitations to the current clinical study model.…”

“…Preclinical studies have suggested that dihydropyridine-type calcium channel antagonists can antagonize dopamine release (Bourson, Gower, Mir, & Moser, 1989). Furthermore, microdialysis studies have shown that cocaine-induced increases in synaptic dopamine concentrations are blocked by two agents of the dihydropyridine class, isradipine and nimodipine, but not by other types of calcium antagonists (Pani et al, 1990).…”

Self-Biting Induced by Activation of L-Type Calcium Channels in Mice: Dopaminergic Influences

“…Instead, it produces a hypokinetic motor syndrome with dystonia [8]. BBay K 8644 exaggerates locomotor responses to cocaine, but does not exaggerate motor behaviors related to amphetamine [5,42]. Therefore, the hypothesis that BBay K 8644 provokes SB and SIB by stimulating a massive release of dopamine is likely to be oversimplified.…”

Comparative Experimental Studies of Calcium Channel Agonists and Antagonists against Ovariectomy Induced Osteoporosis In Rats

“…Group 14 and group 5 OVX animals were treated with Bay-K-8644 (0.05 mg/kg, i.p.). 15 Selected test and standard drug were administered for successive 40 days in-between 9 to 11 AM to avoid effect of fluctuating neuro-hormonal levels on the drugs. On 41 st day various parameters were studied like physical parameters of bone, blood chemistry, histopathological examination and osteoclast count were done.…”