Antagonism of non-NMDA receptors in the dorsal periaqueductal grey induces anxiolytic effect in the elevated plus maze.

Microinjections of glutamate into the dorsal periaqueductal grey (DPAG) of rats induce flight behavior, and blockade of glutamate NMDA receptors in the same region increases exploratory behavior of rats tested on the elevated plus maze. To investigate a possible role of other glutamate receptors in the DPAG on anxiety modulation, rats (n = 6-10) received microinjections into this structure of CNQX (1 and 3 nmol/0.5 microl), an AMPA/kainate antagonist, or GDEE (80 or 160 nmol/0.5 microl), a non-selective glutamate antagonist, and were tested on the elevated plus-maze, an ethologically based animal model of anxiety. Both drugs increased the percentage of entries into open arms, as compared to rats receiving vehicle, without changing the number of enclosed arm entries. Injections of the active compounds outside the DPAG were not effective. The anxiolytic effect of CNQX (3 nmol/0.5 microl) was not reversed by glycine (10 nmol/0.5 microl), injected into the DPAG 5 min after CNQX administration. These results suggest that, in addition to NMDA receptors, non-NMDA glutamate receptors may also modulate anxiety in the DPAG.