N-methyl-D-aspartate receptor blockade impairs behavioural performance of rats in a reaction time task: new evidence for glutamatergic-dopaminergic interactions in the striatum.
The effects of blocking glutamate transmission at the N-methyl-D-aspartate receptor subtype were studied in rats performing a conditioned reaction time motor task. Rats were trained to release a lever after the onset of a visual stimulus within a time limit to obtain food reward. The results showed that the performances of the groups receiving the N-methyl-D-aspartate receptor antagonists dizocilpine maleate (0.1 mg/kg) injected systemically or DL-2-amino-5-phosphonovaleric acid at the highest dose tested (5.0 micrograms/microliter/side) injected locally into the striatum changed significantly as compared to controls. The effects of these antagonists, consisting of an increase in the number of lever releases occurring before the visual stimulus onset ("anticipated responses"), were similar to those induced by injecting dopamine into the same striatal location. Both dizocilpine maleate and DL-2-amino-5-phosphonovaleric acid (5.0 micrograms/microliter) reversed the motor deficits, resulting in an increase in the number of lever releases after the time limit ("delayed responses") that were induced by the D2 dopamine receptor antagonist raclopride. Although these results partly confirm the existence of a functional antagonism between the glutamatergic and the dopaminergic systems in the striatum, opposite findings were obtained with the group that received intrastriatal DL-2-amino-5-phosphonovaleric acid at the lowest dose (0.5 micrograms/microliter/side). When given alone, 0.5 micrograms/microliter DL-2-amino-5-phosphonovaleric acid had no behavioural effects, but when jointly administered with dopamine or raclopride, it was found to reverse the effects of dopamine and to potentiate the motor deficits induced by raclopride. These opposite effects on the reaction time task observed after the intrastriatal injection of DL-2-amino-5-phosphonovaleric acid, depending on the dose tested, occurred only after a combined treatment with a dopaminergic agonist or antagonist and suggest that the level of the striatal dopaminergic activity may play a critical role in regulating the glutamate transmission via the N-methyl-D-aspartate receptors during the performance of complex sensorimotor tasks of this kind.
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Laboratoire associé à l'Université Aix-Marseille II, France.
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Baunez
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Nieoullon
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Amalric
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000033:anatomy & histology / Q000502:physiology*; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; D020891:Raclopride; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D004298:Dopamine