Modulation of defensive responses and anxiety-like behaviors by group I metabotropic glutamate receptors located in the dorsolateral periaqueductal gray

Glutamatergic neurotransmission in the dorsolateral periaqueductal gray (dlPAG) is related to defensive responses. However, the role of group I glutamate metabotropic receptors (mGluR) in these responses has been poorly investigated. The objective of the present study, therefore, was to test the hypothesis that interference with group I mGluR-mediated neurotransmission in dlPAG could modulate defensive responses. Male Wistar rats with cannulae aimed at the dlPAG were submitted to the following experiments: 1. intra dlPAG injections of vehicle (veh, 0.2 μL) or (RS)1-aminoindan-1,5-dicarboxylic acid (AIDA, 30–100 nmol, an mGluR1 receptor competitive antagonist) followed, 5 min later, by veh or trans-(+)-1-amino-1,3-ciclopentanedicarboxylic acid (tACPD, a group I and II mGluR agonist, 30 nmol); 2. intra-dlPAG injections of veh, AIDA (30 nmol) or 2-methyl-6-(phenylethynyl)-pyridine (MPEP, an mGluR5 receptor non-competitive antagonist, 50 nmol) followed by trans-azetidine-2,4-dicarboxylic acid (tADA, a group I mGluR agonist, 10 nmol); 3. and 4. intra-dlPAG injections of vehicle, AIDA (10–30 nmol) or MPEP (10–50 nmol) before the elevated plus maze (EPM) test; 5. intra-dlPAG injections of vehicle, AIDA (30 nmol) or MPEP (50 nmol) before the Vogel punished licking test. tACPD induced defensive responses characterized by jumps and an increased number of crossings in the observation box. These responses were attenuated by AIDA (30 nmol). tADA produced similar responses, although of lower intensity. tADA effects were prevented by AIDA and MPEP. Both drugs also produced anxiolytic-like effects in the EPM and Vogel tests when injected alone. The results suggest that group I metabotropic glutamate receptors in the dlPAG facilitate defensive responses and may also be involved in regulating anxiety-like behavior.