Activation of dorsal periaqueductal gray by glycine produces long lasting hyponociception in rats without overt defensive behaviors

Electrical or glutamate stimulation of the dorsal periaqueductal gray matter (DPAG) of rats induces overt defensive behavior, such as freezing or flight, and hyponociception, while glycine and d-serine, a specific NMDA/GLYB-site ligand, produced only subtle defensive behavior related to risk assessment and avoidance from the open arms in the elevated plus-maze test. In order to verify whether the GLYB site in the DPAG could also be involved in hyponociception, glycine (GLY; 10, 20, 50, and 80 nmol/0.3 µl) and (+/−)-3-amino-1-hydroxy-2-pyrrolidone (HA966; 10 nmol/0.3 µl), a GLYB-site antagonist, were microinjected in rats submitted to the radiant heat-induced tail-flick test. GLY increased tail-flick latencies in a dose-dependent way. This hyponociceptive effect was completely reversed by co-administration with HA966. GLY given in the deep layer of superior colliculus did not produce changes in tail-flick latencies. Therefore, the results suggest that the activation of GLYB receptors in the DPAG is also involved in the hyponociception elicited by this brain area.