Activation of 5-HT2A receptors in the rat prefrontal cortex results in glutamate release (5-HT-induced EPSCs) from thalamocortical afferents (Aghajanian & Marek, 1997 Marek et al., 2001). Activation of both metabotropic glutamate2 receptors (mGluR2) (Marek et al., 2000) and group III mGluR (Lee, Y. et al., 2000, SFN abstr.) suppresses glutamate release from these terminals. The purpose of this study is to investigate whether mGluR4 and/or mGluR8 (group III mGluR) modulate excitatory neurotransmission from these cortical terminals. The group III mGlu antagonist MAP4 suppressed 5-HT-induced EPSCs with an EC50 = 46 µM and maximal suppression of only 29% at 300 µM. MAP4 (300 µM) nearly completely blocked the suppressant action of L-AP4 on 5-HT-induced EPSCs, consistent with a report that MAP4 is a partial agonist at the hmGluR4 (Knopfel et al., 1995). The moderately selective mGluR8 agonist PPG suppressed 5-HT-induced EPSCs with IC50 of ~ 0.4 µM (maximal suppression 93%), though with a shallow slope. The mGlu ...