Endocannabinoid signaling system and brain reward: emphasis on dopamine

The brain's reward circuitry consists of an "in series" circuit of dopaminergic (DA) neurons in the ventral tegmental area (VTA), nucleus accumbens (Acb), and that portion of the medial forebrain bundle (MFB) which links the VTA and Acb. Drugs which enhance brain reward (and have derivative addictive potential) have common actions on this core DA reward system and on animal behaviors relating to its function. Such drugs enhance electrical brain-stimulation reward in this reward system; enhance neural firing and DA tone within it; produce conditioned place preference (CPP), a behavioral model of incentive motivation; are self-administered; and trigger reinstatement of drug-seeking behavior in animals extinguished from drug self-administration. Cannabinoids were long considered different from other reward-enhancing drugs in reward efficacy and in underlying neurobiological substrates activated. However, it is now clear that cannabinoids activate these brain reward processes and reward-related behaviors in similar fashion to other reward-enhancing drugs. This brief review discusses the roles that endogenous cannabinoids (especially activation of the CB1 receptor) may play within the core reward system, and concludes that while cannabinoids activate the reward pathways in a manner consistent with other reward-enhancing drugs, the neural mechanisms by which this occurs may differ.