Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats.
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 after d-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 reduced d-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 of d-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 by d-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.
Ouagazzal
A
A
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Marseille, France.
Nieoullon
A
A
Amalric
M
M
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D003913:Dextroamphetamine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D020891:Raclopride; D016291:Dizocilpine Maleate; D003913:Dextroamphetamine