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Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats

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Abstract

Blocking glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptor complex with MK-801 (0.15–0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed afterd-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1–0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reducedd-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects ofd-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced byd-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.

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  1. Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, 31 chemin J. Aiguier, 13402, Marseille cedex 9, France

    A. Ouagazzal, A. Nieoullon & M. Amalric

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  1. A. Ouagazzal
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  2. A. Nieoullon
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  3. M. Amalric
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Ouagazzal, A., Nieoullon, A. & Amalric, M. Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats. Psychopharmacology 111, 427–434 (1993). https://doi.org/10.1007/BF02253532

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  • DOI: https://doi.org/10.1007/BF02253532

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