Characterisation of mGluRs which modulate nociception in the PAG of the mouse

The contribution of metabotropic glutamate receptors (mGluRs) to the modula tion of nociception by the periaqueductal gray (PAG) matter was investigate d in mice, Intra-PAG microinjection of (1S,3R)-ACPD, an agonist of groups I and II mGluRs, as well as (S)-3,5-DHPG, a selective agonist of group I mGl uRs. increased the latency of the nociceptive reaction (NR) in the hot plat e test. (RS)-AIDA, an antagonist of group I mGluRs, antagonized the effect of (S)-3,5-DHPG, but changed the effect induced by (IS,3R)-ACPD in that a d ecrease in the latency for the NR could now be observed. L-CCG-I and L-SOP, which are agonists of groups II and III mGluRs respectively, decreased the latency; of the NR. (2S)-alpha-EGlu and (RS)-alpha-MSOP, which are antagon ists of groups IT and III mGluRs, respectively, antagonized the effect of L -CCG-I and L-SOP, (RS)-AIDA and (RS)-alpha-MSOP alone decreased and increas ed, respectively, the latency of the NR with the highest doses used. (2S)-a lpha-EGlu alone did not change significantly the latency of the NR. Intra-P AG microinjection of LH, an agonist of ionotropic glutamate receptors, indu ced a dose-dependent analgesia which was blocked by pretreatment with DL-AP 5. a selective antagonist of NMDA receptors. No mGluRs antagonists were abl e to prevent LH-induced analgesia. These results emphasize the possible inv olvement of mGluRs in the modulation of nociception. It seems that activati on of group I mGluRs potentiates, while groups IT and III mGluRs decrease, the activity of the FAG for the modulation of nociception. (C) 1998 Elsevie r Science Ltd. All rights reserved.