Modulation of defensive behavior by periaqueductal gray NMDA/glycine-B receptor.

Glutamate (GLU) associated with glycine, act as co-transmitter at the N-methyl-D-aspartate/glycine-B (NMDA/GLY(B)) receptor. Dorsal periaqueductal gray (dPAG) neurons express NMDA/GLY(B) receptors suggesting a GLU physiological role in mediating the responses elicited by stimulation of this area. Immunohistochemical data provided evidence of a possible correlation among elevated plus-maze (EPM), fear-like defensive behavior, and dPAG activity. The present data show that whereas the NMDA/GLY(B) receptor agonists increased the open-arm avoidance responses in the EPM, the antagonists had the opposite effects. Microinjection of NMDA/GLY(B) receptor agonists within the dPAG during test sessions in the EPM resulted in an enduring learned fear response detected in the retest. Therefore, in addition to the proposed role for the dPAG in panic attacks (escape), these findings suggest that the dPAG can also participate in more subtle anxiety-like behaviors.

Effects of glycine or (+/-)-3-amino-1-hydroxy-2-pyrrolidone microinjections along the rostrocaudal axis of the dorsal periaqueductal gray matter on rats' performance in the elevated plus-maze task.

The effects of glycine (GLY) or (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA966), a GLY receptor antagonist, microinjections into sites along the rostrocaudal axis of the dorsal periaqueductal gray matter (dPAG) were studied in rats placed on the elevated plus maze (EPM). Selective alterations in the open-arm entries (OAEs) or open-arm time (OAT) of the EPM were the indexes of anxiety. HA966 (30 or 100 nmol, 0.3 microl) increased OAEs and OAT in all 3 dPAG sites, suggesting an anxiolytic effect. GLY (80 and 120 nmol, 0.3 microl) selectively reduced OAEs and OAT, suggesting an anxiogenic effect only when injections were given within the caudal dPAG. When administered together, HA966 reversed the anxiogenic effect of 120 nmol GLY, indicating pharmacological selectivity for the effects of GLY on GLY receptors. Results reinforce an involvement of N-Methyl-D-aspartate-coupled GLY receptors in anxiety and suggest that saturation of this receptor may vary along the dPAG.