Abstract
Experiments were carried out in mice to investigate the influence of diazepam (DZP) on dexamphetamine, para-chloro-N-methylamphetamine (pCMA), cocaine, morphine, trihexyphenidyl or (in MAOIs pretreated) reserpine induced motor hyperactivity.
The interaction of DZP with these hyperactivities in which probably different biochemical central mechanisms are involved allows to construct a profile of action of DZP and to approach its mechanism of action. The locomotor hyperactivities induced by dexamphetamine, pCMA, morphine, cocaine were not reduced by DZP even by doses which decrease spontaneous locomotor activity; low doses of DZP enhance the hyperactivity induced by these compounds. Those induced by trihexyphenidyle or by reserpine (after MAOI) were reduced by DZP at doses which produce no decrease in spontaneous motor activity.
Inasmuch as DZP at low doses potentiates the effects of 4 different substances, the results can hardly be satisfactorily explained neither by an interference of the benzodiazepine on the metabolism of the drugs or by a depression of the anxiogenic action of dexamphetamine.
Even though it may be difficult to relate the antagonism of DZP on trihexyphenidyl- or on reserpine- (after MAOI) induced motor hyperactivity to the suggested anticholinergic and dopaminergic actions of DZP, these effects may partly be involved in the increase in locomotor hyperactivity induced by dexamphetamine, morphine or cocaine.
The observed effect of DZP on pCMA induced locomotor hyperactivity does not support a possible antiserotonine action often suggested to explain the effects of benzodiazepines in conflict situations.
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Soubrié, P., Simon, P. & Boissier, J.R. Effets du diazépam sur six modèles d'hyperactivité chez la souris. Psychopharmacologia 45, 197–201 (1975). https://doi.org/10.1007/BF00429061
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DOI: https://doi.org/10.1007/BF00429061