Tolerance to the antinociceptive effect of morphine microinjections into the ventral but not lateral-dorsal periaqueductal gray of the rat

Tolerance to the antinociceptive effect of morphine is mediated at least in part by morphine's action within the periaqueductal gray (PAG). The object ive of the present study was to determine whether both ventral and lateral- dorsal PAG regions contribute to the development of tolerance. It was found that the antinociceptive efficacy of microinjecting morphine (5 mu g/0.4 m u l) into the ventral but not the lateral-dorsal PAG diminished with succes sive injections. Control experiments indicated that this decrease was cause d by tolerance to morphine and was not a result of cell death caused by rep eated microinjections or habituation from repeated behavioral testing. The finding of greater susceptibility of the ventral compared with the lateral- dorsal PAG to the development of tolerance adds to a growing literature dis tinguishing antinociception from these two regions.