Immobility and flight associated with antinociception produced by activation of the ventral and lateral/dorsal regions of the rat periaqueductal gray

It has long been known that the periaqueductal gray (PAG) plays an important role in the modulation of nociception. Given that activation of the lateral FAG also produces wild running and tachycardia, it has been suggested that FAG mediated antinociception is part of an integrated defensive reaction. However, an alternative hypothesis is that these effects are merely a secondary response to aversive brain stimulation. If antinociception and flight reactions are caused by aversive brain stimulation, then these effects should always occur together. The objective of the present study was to determine whether antinociception and locomotion could be dissociated by microinjecting morphine and kainic acid into various subdivisions of the caudal FAG. Non-selective activation of lateral and dorsal regions of the PAC by microinjection of kainic acid produced wild running, while injections into the ventrolateral FAG produced immobility. Microinjection of morphine evoked similar locomotor effects, although the onset to effect was slower with morphine (approximately 5 min vs. 1 min for kainic acid), and the antinociceptive efficacy of microinjecting 0.2 mu l of morphine was less than with kainic acid injections. In fact, microinjection of morphine evoked locomotor effects in the absence of antinociception on 39% of the tests. Increasing the injection volume to 0.4 mu l (dose remained at 5 mu g) greatly enhanced the Likelihood that antinociception and locomotor effects (e.g. running, freezing, circling) occurred simultaneously (79%). These findings indicate that, although distinct locomotor effects are associated with antinociception from the ventral and more dorsal regions of the FAG, antinociceptive and locomotor effects can occur independently. This finding is consistent with the hypothesis that ventral and dorsal regions of the FAG integrate defensive freezing and flight reactions, respectively. (C) 1998 Elsevier Science B.V. All rights reserved.