Antinociception induced by stimulation of ventrolateral periaqueductal gray at the freezing threshold is regulated by opioid and 5-HT2A receptors as assessed by the tail-flick and formalin tests.

It has been suggested that antinociception is part of the animal's defensive reaction to threatening situations. Chemical or electrical stimulation of the ventrolateral portion of the periaqueductal gray (vlPAG) produces both defensive freezing behavior and antinociception, supporting the view that the vlPAG is a critical structure in the coordination of the defensive reaction. The present study indicated that electrical stimulation of the vlPAG, at a current intensity sufficient to induce defensive freezing, caused a decrease in reactivity to a phasic escapable noxious stimulus (as measured in the tail-flick test) and to a tonic, inescapable noxious stimulus (as measured in the formalin test). These antinociceptive effects were reversed by microinjections of the opioid antagonist naltrexone or the specific 5-HT2A receptor antagonist ketanserin into the stimulation sites. These results suggest that (a) activation of neural circuits of the vlPAG, responsible for the production of freezing behavior, reduces the reactivity to nociceptive stimuli (as evaluated by the tail-flick and formalin tests) and that (b) opioid- and 5-HT2A-mediated mechanisms are called into action for regulating the antinociceptive response that accompanies the freezing behavior induced by vlPAG stimulation.