The importance of dopaminergic neurotransmission in the hypermotility response produced by the administration of N-methyl-D-aspartic acid into the nucleus accumbens.
The bilateral injection of N-methyl-D-aspartic acid (NMA) into the nucleus accumbens of rats has been shown to stimulate locomotor activity. This response is antagonized by drugs that interfere with dopaminergic neurotransmission, such as reserpine, alpha-methyl-p-tyrosine (AMPT) and haloperidol, suggesting that NMA may exert its effects by stimulating the release of dopamine (DA) from nerve terminals. To test this hypothesis, the ability of NMA to release endogenous DA from slices of nucleus accumbens, which were incubated in magnesium-free medium was evaluated. It was found that NMA, at concentrations of 0.1 and 1 mM, did not stimulate the release of endogenous DA from slices in magnesium-free normal medium, medium containing pargyline (to inhibit monoamine oxidase) or medium containing methylphenidate (to block the reuptake of released DA). In contrast, both amphetamine (10(-5) M) and a high potassium (20 and 40 mM) stimulated the release of endogenous dopamine. The lack of effect of NMA on the release of endogenous DA was supported by in vivo studies which showed that the injection of NMA into the nucleus accumbens, in a dose that stimulated locomotor activity, did not increase the turnover of dopamine as reflected by an increase in the concentration of DOPAC. In contrast, the direct administration of haloperidol (13 nmol) into the nucleus accumbens produced a marked increase in the concentration of DOPAC. To determine the role of activation of DA receptors in the hypermotility response to NMA, NMA was administered together with subthreshold doses of either DA or apomorphine into the nucleus accumbens of rats pretreated with AMPT.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018492:Dopamine Antagonists; D004338:Drug Combinations; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D016202:N-Methylaspartate; D009714:Nucleus Accumbens / Q000187:drug effects*; D010293:Pargyline / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012686:Septal Nuclei / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D018492:Dopamine Antagonists; D004338:Drug Combinations; D008781:Methyltyrosines; D001224:Aspartic Acid; D016202:N-Methylaspartate; D019805:alpha-Methyltyrosine; D012110:Reserpine; D010293:Pargyline; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D001058:Apomorphine; D011188:Potassium; D004298:Dopamine