Anxiogenic-like effect of glycine and D-serine microinjected into dorsal periaqueductal gray matter of rats.

The glutamatergic system of the dorsal periaqueductal gray matter (DPAG) has been implicated in anxiety. This study shows that microinjections of glycine (GLY) or D-serine (D-SER), into the DPAG of rats, dose-dependently reduced the number of entries and the time spent on open arms of an elevated plus-maze (EPM), an established animal model for measuring anxiety-related behavior. This anxiogenic-like effect was greatest following DPAG application of either 80 nmol GLY or 160 and 320 nmol D-SER. Microinjections of these same amino acid doses outside the DPAG, or of L-serine (320 nmol) inside the DPAG, produced neither of these pro-anxiety effects. The current results suggest that, in vivo, the GLY modulatory site of N-methyl-D-aspartate receptors is not fully saturated, and further substantiate a role for the DPAG excitatory amino acid system in anxiety.