Intracellular recordings were performed from a rat corticostriatal slice preparation in order to characterize the effects of group III metabotropic 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 receptors. Both L-2- amino-4-phosphonobutanoate (L-AP4) and L-serine-O-phosphate (L-SOP) were effective in reducing the amplitude of cortically evoked EPSPs, in a dose- dependent manner. The EC50 value for the effect of L-SOP and L-AP4 was 0.89 μM and 9.95 μM, respectively. Both L-AP4 and L-SOP had negligible effects on the intrinsic membrane properties of the recorded neurons and did not alter the postsynaptic response to focal application of glutamate, suggesting a presynaptic site of action. The presynaptic inhibition of both L-SOP and L- AP4 was fully antagonized by 250 μM (s)-2-methyl-2-amino-4- phosphonobutanoate (MAP4), whilst it was unaffected by 500 μM RS-methyl-4- carboxyphenylglycine (MCPG). Conversely, the presynaptic inhibitory effect on the EPSP amplitude exerted by 10 μM IS,3R-l-aminocyclopentane-l, 3- dicarboxylic acid (IS,3R-ACPD) was antagonized by 500 'μM MCPG, whilst it was not blocked by 250 μM MAP4. Finally, the reduction of the EPSP amplitude produced by a saturating dose of L-SOP was further increased by 10 'aM I S,3R-ACPD, suggesting an additive effect of these compounds. The present results are consistent with the idea that group III mGluRs exert a presynaptic inhibitory modulation of the excitatory glutamatergic transmission at corticostriatal synapses.
- L- SOP
- Metabotropic glutamate receptor
- Presynaptic inhibition
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Drug Discovery