Differential Control by N‐Methyl‐D‐Aspartate and Kainate of Striatal Dopamine Release In Vivo: A Trans‐Striatal Dialysis Study

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Abstract
Using the technique of transstriatal dialysis in halothane-anesthetized rats, we have studied the effects of intrastriatally infused N-methyl-D-aspartate (NMDA), kainate, and quisqualate on the liberation of endogenous striatal dopamine. The striatal infusion of NMDA (10-3-10-2M) or kainate (10-4-10-2M) but not of quisqualate (up to 10-2M) for one 20-min fraction provoked a dramatic increase in striatal dopamine efflux up to a maximum of 1,200 and 3,400% of basal levels for NMDA and kainate, respectively. NMDA (10-3M) evoked liberation of striatal dopamine was totally blocked by coinfusion of 2-amino-5-phosphonovalerate (2-APV; 5 × 10-4M) and by the systemic injection of phencyclidine (3 mg/kg i.p.). The effects of NMDA (10-3M) were also totally antagonized in a dose-dependent manner by the striatal coinfusion of atropine (10-7-10-4M), and abolished in rats that had received bilateral striatal ibotenate lesions (10μg/1μl) 1 week prior to implantation of the dialysis fiber. The striatal infusion of tetrodotoxin (10-6M) reduced basal dopamine efflux by 60–70% and abolished the NMDA (10-3M)-evoked liberation of striatal dopamine. The effects of kainate (10-3M) on striatal dopamine efflux were only partially reduced by doses of 2-APV or atropine that totally blocked the NMDA response, and were also partially resistant to tetrodotoxin. The intrastriatal infusion of carbachol (10-3M) for one 20-min fraction was without effect on striatal dopamine efflux; 10-2M carbachol produced a 50% increase in dopamine release in the fraction following carbachol application. The present results indicate that the effects of NMDA on striatal dopamine release are likely to be mediated via an active cholinergic striatal neuron which seems to play a permissive rather than an active role in this effect. The effects of kainate may involve a direct action on dopa-minergic terminals as well as activation of polysynaptic pathways or liberation of an endogenous NMDA receptor agonist.