MUSCARINIC RECEPTORS REGULATE EXTRACELLULAR GLUTAMATE LEVELS IN THE RAT STRIATUM - AN IN-VIVO MICRODIALYSIS STUDY

Regulation of extracellular glutamate levels by muscarinic receptors i n the striatum of unanesthetized rats was investigated by microdialysi s. Extracellular glutamate levels were elevated by intrastriatal perfu sion of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a com petitive substrate of plasma membrane excitatory amino acid transporte rs. The nonselective muscarinic agonist, oxotremorine (0.5-54 mu M) si gnificantly decreased L-trans-PDC-evoked glutamate levels in a concent ration-dependent manner. Scopolamine (0.1-10 mu M), a nonselective mus carinic receptor antagonist, reversed the effect of oxotremorine, whic h confirms that muscarinic receptor activation mediated the reduction of L-trans-PDC-evoked glutamate levels. In addition, scopolamine (10 m u M) significantly elevated basal extracellular glutamate levels, an e ffect prevented by oxotremorine, which suggests that acetylcholine ton ically regulates glutamatergic transmission in the striatum. Previous data from this laboratory have shown that L-trans-PDC-evoked glutamate levels are partially calcium-dependent. The present study demonstrate d that attenuation of L-trans-PDC-evoked glutamate levels by reduced c alcium was not altered by oxotremorine. Therefore, it is likely that m uscarinic receptors regulate calcium-dependent glutamate release evoke d by L-trans-PDC.