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 microL) 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.     

Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses

The medial division of the central nucleus of the amygdala (CeA_M) and the lateral division of the bed nucleus of the stria terminalis (BNST_L) are closely related. Both receive projections from the basolateral amygdala (BLA) and both project to brain areas that mediate fear-influenced behaviors. In contrast to CeA_M however, initial attempts to implicate the BNST in conditioned fear responses were largely unsuccessful. More recent studies have shown that the BNST does participate in some types of anxiety and stress responses. Here, we review evidence suggesting that the CeA_M and BNST_L are functionally complementary, with CeA_M mediating short- but not long-duration threat responses (i.e., phasic fear) and BNST_L mediating long- but not short-duration responses (sustained fear or ‘anxiety’). We also review findings implicating the stress-related peptide corticotropin-releasing factor (CRF) in sustained but not phasic threat responses, and attempt to integrate these findings into a neural circuit model which accounts for these and related observations.