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Abstract
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 microM and 9.95
microM, 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 microM (s)-2-methyl-2-amino-4-phosphonobutanoate
(MAP4), whilst it was unaffected by 500 microM RS-methyl-4-carboxyphenylglycine (MCPG).
Conversely, the presynaptic inhibitory effect on the EPSP amplitude exerted by 10
microM 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) was antagonized
by 500 microM MCPG, whilst it was not blocked by 250 microM MAP4. Finally, the reduction
of the EPSP amplitude produced by a saturating dose of L-SOP was further increased
by 10 microM 1S,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.