Release of endogenous cannabinoids from ventral tegmental area dopamine neurons and the modulation of synaptic processes

• The literature regarding the role of endogenous cannabinoids in brain reward circuits is reviewed.
• We propose that endogenous cannabinoids are released from mid-brain dopamine neurons during periods of increased excitability.
• We propose that endocannabinoids act within the ventral mid-brain to regulate dopamine function in the forebrain.
• We propose that the reward enhancing ability of abused drugs is partly mediate by the actions of endogenous cannabinoids in the ventral midbrain.

Endogenous cannabinoids play important roles in a variety of functions in the mammalian brain, including the regulation reward-related information processing. The primary mechanism through which this is achieved is the presynaptic modulation of synaptic transmission. During reward- and reinforcement-related behavior dopamine levels increase in forebrain areas and this has recently been shown to be modulated by the endocannabinoid system. Therefore, understanding how endocannabinoids are mobilized to modulate synaptic inputs impinging on midbrain dopamine neurons is crucial to a complete understanding of the roles that these molecules play in reward behavior, drug abuse and addiction. Here we summarize the literature describing short-term and long-term regulation of afferent connections on dopamine neurons in the ventral tegmental area via endocannabinoid activation of cannabinoid CB1 receptors, and describe the mechanisms through which these molecules are released during reward-based behavior and exposure to abused drugs.