Systematic examination in the rat of brain sites sensitive to the direct application of morphine: observation of differential effects within the periaqueductal gray.

An extensive mapping of the rat brain (403 sites) ranging from AP +8 to AP -3 revealed that the region showing maximum sensitivity to the intracerebral administration of morphine in the elevation of the nociceptive threshold lay within the periaqueductal gray. Analysis of the distribution of responsive sites indicated that the most active sites, those having the shortest latency of effect, were located within the ventrolateral aspect of the caudal periaqueductal gray. These antinociceptive actions of morphine were observed to be both dose-dependent and reversible by the administration of naloxone. We observed that microinjections of morphine could produce changes in the pinch withdrawal response which were distributed in a crude somatotopic fashion. Injections into the rostral aspect of the periaqueductal gray yielded a block of the pinch response in the rostral portions of the body, whereas such injections into the caudal periaqueductal gray always yielded a whole body analgesia. In the rostral sites, transient ipsilateral blocks of the pinch response were occasionally seen. A pinch block limited to the hind paws alone was never observed. It is suggested that morphine acting through the periaqueductal gray may actuate a potent supraspinal modulatory system related to the transmission of information derived from behaviorally aversive stimuli.