GLUTAMATE RECEPTORS OF A QUISQUALATE-KAINATE SUBTYPE ARE INVOLVED IN THE PRESYNAPTIC REGULATION OF DOPAMINE RELEASE IN THE CAT CAUDATE-NUCLEUS INVIVO

Experiments were conducted with halothane‐anesthetized cats implanted with a push‐pull cannula in the caudate nucleus in order to estimate the effects of glutamate (GLU) agonists on the release of 3H‐dopamine continuously synthesized from 3H‐tyrosine. In the presence of tetrodotoxin (TTX), glutamate (10−8 M, 10−4 M) and kainate (KAI) (10−5 M) stimulated the release of 3H‐dopamine while quisqualate (10−5 M) and N‐methyl‐D‐aspartate (NMDA) (10−5 M) were without effect. The stimulatory effect of kainate (10−5 M) on 3H‐dopamine release did not seem to be mediated by glutamate released from corticostriatal fibers, as not only kainate, but also quisqualate (QUI) and N‐methyl‐D‐aspartate enhanced the efflux of glutamate through a tetrodotoxin‐resistant process. Riluzole (10−5 M), gamma‐D‐glutamyl‐glycine (GDGG) (10−5 M) and glutamine‐diethyl‐ester (10−5 M) prevented the stimulatory effect of kainate (10−5 M) while 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX) (10−5 M), kynurenate (10−5 M) and 2‐amino‐5‐phosphonovalerate (APV) (10−5 M) were without effect. In the presence of concanavalin A (CONA) (10−7 M), a lectin which is known to prevent the quisqualate‐evoked desensitization of glutamate receptors, quisqualate (10−5 M) stimulated the release of 3H‐dopamine. In addition, in the absence of concanavalin A, quisqualate (10−5 M) blocked the stimulatory effects of kainate (10−5 M) or glutamate (10−4 M) on 3H‐dopamine release. These results suggest the involvement of receptors of the quisqualate/kainate subtype in the direct glutamate‐induced presynaptic facilitation of dopamine release. In contrast to what was observed in the presence of tetrodotoxin, in the absence of the neurotoxin, high concentrations of glutamate (10−4 M) and kainate (10−5 M) reduced rather than stimulated the release of 3H‐dopamine. A weak inhibitory effect was also observed with quisqualate (10−5 M) while N‐methyl‐D‐aspartate (10−5 M) was without effect. In the light of previous studies, these latter observations suggest that glutamate can also exert an indirect inhibitory presynaptic influence on the release of dopamine from nerve terminals of the nigrostriatal dopaminergic neurons by acting on receptors of the quisqualate/kainate subtype located on striatal GABAergic neurons. Copyright © 1990, Wiley Blackwell. All rights reserved