Nifedipine and flunarizine block amphetamine-induced behavioral stimulation in mice

Grebb, Jack A.

doi:10.1016/0024-3205(86)90605-3

Cited by 61 publications

(24 citation statements)

References 14 publications

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“…In fact, KB-2796 as well as nicardipine, which is the weakest displacer of [3H]spiperone bind ing in the present experiment, inhibit metham phetamine-induced locomotion and circling in mice (17). This kind of inhibitory effect has also been reported with other calcium antago nists such as flunarizine and nifedipine (21) and verapamil (22). In amphetamine-induced circling, calcium is supposed to play an impor tant role (22).…”

Section: In Vitro Effects Of Calcium Antagonists On [3hjspiperone Binsupporting

confidence: 67%

Neurochemical Investigation on the Effects of a New Diphenylpiperazine Calcium Antagonist, KB-2796, on the Central Dopaminergic System of Rats.

Akira¹,

Ozaki²,

Hara³

et al. 1992

Jpn.J.Pharmacol

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-The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the striatal dopaminergic system of rats were investigated in comparison with var ious calcium antagonists and the dopamine antagonist chlorpromazine. The inhibiting effect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was weaker than those of chlorpromazine and the other diphenylpiperazine analogues, flunarizine and cinnarizine, and more potent than those of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) had no effect on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes obtained from the rat at 36 hr and 7 days after repeated administration for 18 days, whereas flu narizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased Bmax values by 47% and 31%, respectively, at 36 hr, but not at 7 days after the final administra tion. At 1 hr after the single administration, KB-2796 (30, 100 mg/kg, p.o.) had no effect on the content of dopamine and its metabolites in the striatum, whereas flunar izine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased the level of homovanillic acid. These results indicate that flunarizine may affect dopaminergic neurotransmission by partially blocking dopamine D2 receptors, while KB-2796 has negligible in vivo effect on the dopaminergic system.

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Section: In Vitro Effects Of Calcium Antagonists On [3hjspiperone Binsupporting

confidence: 67%

Neurochemical Investigation on the Effects of a New Diphenylpiperazine Calcium Antagonist, KB-2796, on the Central Dopaminergic System of Rats.

Akira¹,

Ozaki²,

Hara³

et al. 1992

Jpn.J.Pharmacol

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“…Fung & Uretsky (1980) have shown that intrastriatal injection of EGTA could inhibit amphetamine-induced rotation in mice. Also, Grebb (1986) has demonstrated that nifedipine can antagonise amphetamine-induced hyperactivity. However, the specificity of these effects to the dopamine releasing ability of amphetamine is questionable; the effects seen by Grebb (1986) occurred at doses higher than those we have used and are possibly due to other effects of calcium antagonists that are seen at high doses (De Feudis, 1987).…”

Section: Discussionmentioning

confidence: 99%

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

Bourson¹,

Gower

Mir³

et al. 1989

British J Pharmacology

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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.

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“…Taken together, these data suggest that the antireinforcing effect of isradipine may be more related to interference with the reward and less with drivelike effects of amphetamine. Similar reasoning applies to verapamil, a phenylalkylamine CCI reported to be a potent antagonist of amphetamine-induced place preference without intrinsic aversive or reinforcing properties (Pucilowski et al 1993) and devoid of inhibitory activity against amphetamine-induced locomotor stimulation (Grebb 1986;Mecke et al 1991;Renwart et al 1986). …”

Section: Discussionmentioning

confidence: 99%

“…Thus, it has been argued that this property of CCis may account for their ability to attenuate the drive (locomotion) and reward (place preference, self-administration) effects of cocaine. Interestingly enough, various CCis have been generally ineffective in antagonizing amphetamine-induced dopamine release (Pani et al 1990) or locomotor stimulation (Ansah et al 1993;Grebb 1986;Martin-Iverson et al 1993;Mecke et al 1991;Moore et al 1993;Renwart et al 1986). It has been thus hypothesized that there is a causal relationship between the inability of CCis to interfere with either effect of amphetamine.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly enough, amphetamine-induced locomotor stimulation in mice is suppressed by high, sedative doses of some dihydropyridine CCis (darodipine, nicardipine, nifedipine) (Grebb 1986;Renwart et al 1986) but not the others (nimodipine, nitrendipine, nisoldipine) (Grebb 1986). In our previous study, we demonstrated that verapamil, a phenylalkylamine CCI reportedly devoid of antagonistic action against either amphetamine- (Grebb 1986;Renwart et al 1986) or cocaine-induced locomotor stimulation (Mecke et al 1991;Pani et al 1990), significantly suppressed amphetamine-induced conditioned place preference (Pucilowski et al 1993). Verapamil also failed to affect side preference on its own, indicating that it does not have aversive or rewarding properties in this paradigm.…”

Section: Open Field Amphetamine Increased the Open Field Activity Bumentioning

confidence: 99%

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Isradipine Suppresses Amphetamine-Induced Conditioned Place Preference and Locomotor Stimulation in the Rat

Pucilowski

Płaźnik

Overstreet

1995

Neuropsychopharmacology

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The locomotor activating and the reinforcing effects of psychomotor stimulants are considered to be correlated with and responsible for the development and maintenance of stimulant addiction. Experiments were conducted to examine the effects of isradipine, the L-type calcium channel inhibitor, on the d-amphetamine-inducedinduced conditioned place preference in rats (Pani et al. 1991;Pucilowski et al. 1993) and to suppress intravenous cocaine self-administration in rats (Martellotta et al. 1994) and mice (Kuzmin et al. 1992). The positive reinforcing properties of psychomotor stimulants are thought to be directly correlated with their ability to induce locomotor stimulation (Wise 1990). It is hypothesized that effective pharmacological treatment for drug abuse should suppress conditioned responses, that is, reinforcing and locomotor stimulant effects, to a greater extent than the acute effects of addictive drugs. This is because potent acute antireinforcing or aversive effects of a therapeutic drug would likely compromise the necessary patient compliance with the therapy (Hursh 1993).The ability of dihydropyridine CCis (e.g., isradi-0893-133X/95/$9 .50 SSDI 0893-133X(94)00080-J

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Nifedipine and flunarizine block amphetamine-induced behavioral stimulation in mice

Cited by 61 publications

References 14 publications

Neurochemical Investigation on the Effects of a New Diphenylpiperazine Calcium Antagonist, KB-2796, on the Central Dopaminergic System of Rats.

Neurochemical Investigation on the Effects of a New Diphenylpiperazine Calcium Antagonist, KB-2796, on the Central Dopaminergic System of Rats.

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

Isradipine Suppresses Amphetamine-Induced Conditioned Place Preference and Locomotor Stimulation in the Rat

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