METABOTROPIC GLUTAMATE-RECEPTOR AGONISTS REDUCE PAIRED-PULSE DEPRESSION IN THE DENTATE GYRUS OF THE RAT IN-VITRO

We have analyzed the effects of agonists acting at different classes of metabotropic glutamate receptors (mGluRs) on paired pulse depression (PPD) at the medial perforant path/granule cell synapse. Drugs were bath applied and paired pulses delivered at 3-min intervals during control and during drug application. Both 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 100 mu M), which acts at class I (mGluR1, 5) and class II (mGluR2, 3) mGluRs and L-2-amino-4-phosphobutyric acid (L-AP4, 100 mu M) which is specific for class III (mGluR4, 6-8) mGluRs, strongly reduced PPD with an interstimulus interval (ISI) of 40 ms (P < 0.001). The class I specific agonists trans-azetidine-2,4,dicarboxylic acid (t-ADA, 100 mu M) and 3,5,dihydroxyphenylglycine (DHPG, 100 mu M) did not affect PPD. The relatively specific class II agonists S-3-carboxy-4-hydroxyphenylglycine (3C4HPG) and 2S,3S,4S-alpha-carboxycyclopropyl-glycine (L-CCG-I) did reduce PPD, but only at very high concentrations (500 and 40 mu M respectively) with respect to their EC(50) values. These results suggest that two types of mGluRs control PPD at this synapse - a class III mGluR and a class II-like mGluR, which may not correspond to one of the currently cloned receptors.