Group 1 and 2 metabotropic glutamate receptors play differential roles in hippocampal long-term depression and long-term potentiation in freely moving rats

Abstract

This study examined the role of metabotropic glutamate receptors (mGluRs) in hippocampal long-term depression (LTD) in vivo. The group 1 mGluR antagonist (S)4-carboxyphenylglycine (4CPG), group 1/2 antagonist (RS)-α- methyl-4-carboxyphenylglycine (MCPG), and group 2 antagonists (RS)-α- methylserine-O-phosphate monophenyl ester (MSOPPE) and (2S)-α-ethylglutamic acid (EGLU) were used. The NMDA receptor antagonist D(-)-2-amino-5- phosphonopentanoic acid (AP5) was used to examine the NMDA receptor contribution to the observed LTD. Adult male Wistar rats underwent implantation of stimulating and recording electrodes into the Schaffer collaterals and CA1 stratum radiatum, respectively. After recovery of 5-7 d, the field EPSP was measured from freely moving animals. Drugs were applied either before or after 1 Hz low-frequency train (LFT) or 100 Hz stimulation via a cannula implanted in the lateral cerebral ventricle. Nine hundred pulses at 1 Hz produced an LTD that was marked and long-lasting. This LTD was completely inhibited by pre-LFT application of AP5. MCPG inhibited LTD from 2 hr post-LFT. 4CPG partially impaired LTD. MSOPPE and EGLU completely blocked induction of LTD although short-term depression remained intact. MSOPPE did not block long-term potentiation (LTP) induced by 100 Hz stimulation, whereas 4CPG produced a significant inhibition. When MSOPPE was present, LTD could not be induced either before or after LTP induction, whereas LTD could be induced in an identical protocol in vehicle-injected animals. These results suggest a differential role for mGluRs in NMDA receptor-dependent hippocampal LTD in vivo. Group 1 mGluRs may play a role in both LTD and LTP, whereas group 2 mGluRs may be critically involved only in LTD induction.