Locomotor activation induced by MK-801 in the rat: postsynaptic interactions with dopamine receptors in the ventral striatum.
The effects of bilateral 6-hydroxydopamine-induced destruction of the dopamine nerve terminals in the ventral striatum (nucleus accumbens) or pharmacological blockade of dopamine receptors with haloperidol injected locally into this area were examined on the locomotor hyperactivity induced by systemic administration of the non-competitive NMDA receptor antagonist, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5,10-imine hydrogen maleate salt). The locomotor stimulation induced by two doses of MK-801 (0.15 and 0.3 mg/kg, i.p.) was not attenuated by 6-hydroxydopamine bilateral lesions to the ventral striatum, either 7 or 14 days after the operation. The same lesion however reduced the locomotor activation induced by 0.5 mg/kg d-amphetamine 14 days after surgery. Bilateral intra-accumbens injection of haloperidol at a dose (2.5 micrograms/side) that blocked d-amphetamine-induced hypermotility did not reduce the locomotor response to 0.3 mg/kg MK-801, while 5 micrograms/side haloperidol decreased the MK-801-induced locomotor stimulation. These results suggest that the locomotor response to MK-801 is dependent on an interaction between dopaminergic and excitatory amino acid transmission occurring postsynaptically rather than presynaptically in the ventral striatum.
Ouagazzal
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A
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Marseille, France.
Nieoullon
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A
Amalric
M
M
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D018492:Dopamine Antagonists; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D000661:Amphetamine; D006220:Haloperidol; D004298:Dopamine