Cannabinoid transmission and reward-related events

The reward/reinforcement circuitry of the mammalian brain consists of synap tically interconnected neurons associated with the medial forebrain bundle, linking the ventral tegmental area, nucleus accumbens, and ventral pallidu m. Electrical stimulation of this circuit supports intense self-stimulation in animals and, in humans, produces intense pleasure or euphoria. This cir cuit is strongly implicated in the neural substrates of drug addiction and in such addiction-related phenomena as withdrawal dysphoria and craving. Th is circuit is also implicated in the pleasures produced by natural rewards (e.g., food, sex). Cannabinoids are euphorigenic in humans and have addicti ve liability in vulnerable persons, but were long considered "anomalous" dr ugs of abuse, lacking pharmacological interaction with these brain reward s ubstrates. It is now clear, however, that cannabinoids activate these brain substrates and influence reward-related behaviors. From these actions, pre sumably, derive both the abuse potential of cannabinoids and the possible c linical efficacy in dysphoric states. (C) 1998 Academic Press.