It was previously shown that the metabotropic glutamate (mGlu) receptor agonist 1S,3R-ACPD had a variety of actions in rat somatosensory cortex, prominent among them was a depression of synaptic responses (Cahusac, 1994). The present study used intracellular recordings to determine whether the depression was due to an action at pre- or postsynaptic receptors. Male Wistar-derived rats (N = 5, 346 – 567g) were anaesthetized with urethane (2g/kg I.P.). At the end of the experiment they were humanely killed by anaesthetic overdose. Intracellular recordings were made from cortical neurones using pipettes filled with 1.6M K citrate. The recording pipette was glued to a 7-barrelled iontophoresis pipette such that the recording pipette protruded 60 μm ahead of the iontophoresis pipette tip. Different iontophoresis barrels contained one of the following: monosodium L-glutamate (0.5 M, pH 8.5), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 0.1 M, pH 8), (RS)-4-Carboxy-3-hydroxyphenylglycine (4C3HPG, 0.1 M, pH 8.5), α-methyl-(2S,3S,4S)-2-(Carboxycyclopropyl)glycine (MCCG, 0.05 M, pH 8.8), GABA (0.5 M, pH 3.5), Pontamine Sky Blue dye (2% in 0.5 M Na acetate) and 1 M NaCl (for current balancing and current controls). Stimuli consisted of brief (3 – 10 ms) deflections of selected vibrissae by piezoelectric bimorphs. A total of 7 cells were recorded from for sufficient time to evaluate the effects of the agonists. In 6 of 7 cells tested, synaptic transmission was depressed by mGlu agonists. This was associated with complete abolition of EPSPs, suggestive of a presynaptic action. Typically, there were no marked changes in membrane potential (mean before = -53.8±2.45 mV, mean during drug = -54.5±2.98 mV, mean change = 0.70±0.65 mV, t(3) = 1.07, P = 0.365). In contrast when tested with GABA, synaptic depression was associated with the continued presence of EPSPs, indicating a postsynaptic action. The depressant effect produced by 1S,3R-ACPD was reversibly antagonised by the Group II mGlu receptor antagonist MCCG. These results suggest that the depression of synaptic transmission by mGlu receptor agonists is due to an action at Group II mGlu receptors situated on presynaptic terminals (Schoepp, 2001).