The dopaminergic network of the periaqueductal grey was described several years ago (Lindvall & Björklund, 1974). However, considering the key role of dopamine in opiate addiction, it is surprising that the dopaminergic network of the periaqueductal grey area has been ignored in drug reinforcing studies. The objectives of the study were threefold: (i) to further describe the morphological characteristics of the mesencephalic part of the dopaminergic network of the periaqueductal grey (mPAG) in rats, (ii) to discern if these dopaminergic cells are activated after heroin administration (500 µg kg^-1 S.C.), and (iii) to establish the effects of selective lesions of the DA neurons of the mPAG on heroin-induced reward (as measured through conditioned place preference) and locomotor sensitization. At the end of the experiments the animals were humanely killed.

The mesencephalic periaqueductal grey network was observed to be composed of three types of dopaminergic cells putting out fibres mostly running in the periaqueductal grey, after immunohistochemistry. These dopaminergic cells were activated following drug treatment, since they expressed c-Fos after heroin (in comparison with saline-treated rats). Finally, following dopamine depletion of the mPAG (52.7 % dopamine cell loss through cell counting, 80.7 % reduction of in vitro dopaminergic peak as measured through voltammetry), conditioned place preference to heroin was abolished in lesioned rats (P < 0.05, Wilcoxon test), but not heroin-induced sensitization.

The present study provides evidence that the dopaminergic network of the mesencephalic periaqueductal grey is activated by heroin and controls the rewarding effects of this opiate drug. This dopaminergic system should be included as critical for opiate-induced reinforcement, apart from the mesocorticolimbic system.

This study was supported by Spanish Ministerio de Educacion y Cultura (PM98-015), and Plan Andaluz de Investigacion (CVI-127).