Summary
Inhibition of catecholamine synthesis byα-methyl paratyrosine (α-MT) was previously shown to potentiate the behavioral suppression caused by dopamine-receptor antagonists. This effect ofα-MT is in all probability due to inhibition of the compensatory increase in dopamine turnover induced by the dopamine receptor antagonists. In the present study we investigated the effect of theα 2-adrenoreceptor agonist clonidine on the haloperidol-induced suppression of food-reinforced lever-pressing behavior (fixed ratio 40∶1) in rats. Small behaviorally inactive doses of clonidine were found, in analogy withα-MT, to enhance the haloperidol-induced suppression of the lever-pressing behavior. The haloperidol-induced increase in dopamine synthesis (measured as the accumulation of DOPA after inhibition of aromatic amino acid decarboxylare) was antagonized by clonidine in the striatum as well as in the dopamine rich limbic regions. Prazosin, a selectiveα 1-adrenoreceptor antagonist had no effect on the clonidine induced behavioral changes. Idazoxane, a selectiveα 2-adrenoreceptor antagonist, counteracted both the behavioral and biochemical effects of clonidine, indicating that these effects of clonidine are mediated via its action onα 2-adrenoreceptors. The present findings provide support for the notion thatα 2-adrenoreceptors may participate in the regulation of nigro-striatal as well as meso-limbic dopaminergic activity. It is suggested thatα 2-adrenoreceptor agents, especially in combination with classical antipsychotics, might be of therapeutic value in the treatment of disorders associated with abnormal dopaminergic activity.
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Engel, J.A., Johannessen, K., Liljequist, S. et al. Activation of α2-adrenoreceptors enhances haloperidol-induced suppression of operant behavior. J. Neural Transmission 66, 107–120 (1986). https://doi.org/10.1007/BF01260906
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DOI: https://doi.org/10.1007/BF01260906