The effects of L-AP4 and L-serine-O-phosphate on inhibition in primary somatosensory cortex of the adult rat in vivo

The effects of two iontophoretically applied Group III mGluR agonists were studied on the inhibition in neocortex produced by natural stimulation of vibrissae. The agonists L-AP4 and L-serine-O-phosphate (L-SOP) were shown to produce qualitatively similar effects on the inhibition. Forty-four percent of neurones (total n = 57) displayed disinhibition during application of the agonists. The disinhibitory effects often outlasted the offset of the agonist application by at least 10 min. Concurrent application of the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG) appeared to reverse the disinhibitory effects of L-AP4 and L-SOP in 3 out of 5 neurones tested. However (+)-MCPG itself was found to have disinhibitory effects in some neurones. Some neurones (n = 7) showed increases in inhibition during either L-AP4 or L-SOP application. These appeared most pronounced in those neurones where the initial (pre-drug) inhibition was minimal, perhaps suggesting that the agonists were disinhibiting a local disinhibition. The data obtained in the experiments suggest that the disinhibitory effects are mediated by a heteroreceptor on inhibitory terminals, action at which depresses the release of inhibitory transmitter. The possible role of the modulation of inhibition by presynaptic mGluRs is discussed.