Endocannabinoid-dopamine interactions shape ethologically relevant behavior through computation of conditioned stimuli

Abstract

Endocannabinoids are theorized to modulate cue-motivated behavior by amplifying dopamine release within the mesolimbic dopamine system. Here, we summarize the neurochemical results that revealed how endocannabinoids, particularly 2-arachidonoylglycerol within the ventral tegmental area, augment cue-evoked dopamine release events into the nucleus accumbens while concurrently facilitating cue-motivated behavior. Data are initially described within the context of the classical role attributed to the mesolimbic system-promoting reward seeking. We then expand our discussion beyond simple reward-directed behaviors by discussing a potential role for endocannabinoid-mesolimbic dopamine interactions in: switching an animal’s motivation from feeding to foraging behavior when reward availability is temporally delayed, facilitating the extinction of fear memories by amplifying dopaminergic updates of the association between aversive stimuli and their predictors to the fear network, and promoting the avoidance of harmful stimuli through newly discovered negative reinforcement mechanisms.