Glutamate Metabotropic Receptor Agonists Depress Excitatory and Inhibitory Transmission on Rat Mesencephalic Principal Neurons

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Abstract
Lntracellular and whole‐cell patch‐clamp recordings were used to evaluate the actions of different metabotropic glutamate receptor (mGluR) agonists on the synaptic inputs evoked on principal cells of the rat mesencephalon. Bath application of the group Ill mGluR agonists l‐2‐amino‐4‐phosphonobutyric acid (l‐AP4) and l‐serine‐O‐phosphonobutanoate (l‐SOP) did not change the holding current of the cells held at resting potential (‐60 mV) but produced a dose‐dependent inhibition of the amplitude of the excitatory and inhibitory events. l‐AP4 and l‐SOP were more effective at inhibiting the excitatory postsynaptic currents (EPSCs) than the GABAA and GABAB inhibitory postsynaptic currents (IPSCs). The suppressing effects of l‐AP4 and l‐SOP were antagonized by (S)‐2‐amino‐2‐methyl‐4‐phosphonobutanoic acid (MAP‐4) but not by ±‐α‐methyl‐4‐carboxyphenylglycine (MCPG). Moreover, the group II agonist (2S, 1′S, 2′S)‐(carboxycyclopropyl)glycine (l‐CCG1) and the group I agonist (RS)‐3,5‐dihydrophenylglycine (3,5‐DHPG) depressed in a dose‐related manner the EPSC, the GABAA IPSC and the GABAB IPSC. The suppressing effect of the two mGluRs agonists was partially antagonized by MCPG but not by MAP‐4. In addition, both l‐CCG1 and 3,5‐DHPG caused an inward shift of the holding current. To characterize the site of action of the metabotropic receptor agonists, experiments were performed to examine the amplitude and ratio of EPSC and GABAA IPSC pairs. The increase of the s2/sl ratio caused by the agonists suggests that the location of the inhibitory mGluRs was presynaptic. These results indicate that the activation of presynaptic mGluRs controls the release of excitatory and inhibitory transmitters on presumed dopaminergic cells within the ventral mesencephalon.