ACTIVATION OF GROUP-III METABOTROPIC GLUTAMATE RECEPTORS DEPRESSES GLUTAMATERGIC TRANSMISSION AT CORTICOSTRIATAL SYNAPSE

Intracellular recordings were performed from a rat corticostriatal sli ce preparation in order to characterize the effects of group III metab otropic glutamate receptor (mGluR) agonists on excitatory transmission at corticostriatal synapses. The amplitude of excitatory postsynaptic potentials (EPSPs), evoked by cortical stimulation, was significantly decreased by agonists acting at group III metabotropic glutamate rece ptors. Both L-2-amino-4-phosphonobutanoate (L-AP4) and L-serine-O-phos phate (L-SOP) were effective in reducing the amplitude of cortically e voked EPSPs, in a dose-dependent manner. The EC50 value for the effect of L-SOP and L-AP4 was 0.89 mu M and 9.95 mu M, respectively. Both L- AP4 and L-SOP bad negligible effects on the intrinsic membrane propert ies of the recorded neurons and did not alter the postsynaptic respons e to focal application of glutamate, suggesting a presynaptic site of action. The presynaptic inhibition of both L-SOP and L-AP4 was fully a ntagonized by 250 mu M (s)-2-methyl-2-amino-4-phosphonobutanoate (MAP4 ), whilst it was unaffected by 500 mu M RS-methyl-4-carboxyphenylglyci ne (MCPG). Conversely, the presynaptic inhibitory effect on the EPSP a mplitude exerted by 10 mu M 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) was antagonized by 500 mu M MCPG, whilst it was not blocked by 250 mu M MAP4. Finally, the reduction of the EPSP amplitud e produced by a saturating dose of L-SOP was further increased by 10 m u M 1S,3R-ACPD, suggesting an additive effect of these compounds. The present results are consistent with the idea that group III mGluRs exe rt a presynaptic inhibitory modulation of the excitatory glutamatergic transmission at corticostriatal synapses. (C) 1997 Elsevier Science L td.