Cannabinoid regulation of opiate motivational processing in the mesolimbic system: the integrative roles of amygdala, prefrontal cortical and ventral hippocampal input pathways

•Cannabinoid and opioid systems interact during opiate reward processing.•Cannabinoids modulate the rewarding and aversive motivational properties of opiates.•Cannabinoid receptor transmission controls motivational and contextual information inputs to the mesolimbic dopamine system.•Cannabinoid transmission can modulate mesolimbic activity states and motivational processing through a wide variety of neurobiological mechanisms.

Opiates, like many drugs of abuse, possess both rewarding and aversive stimulus properties. Nevertheless, the precise neurobiological mechanisms controlling these different motivational aspects of opiates are not well understood. The brains cannabinoid receptor system shares considerable functional and anatomical overlap with the opiate receptor system and importantly, has been shown to modulate functional inputs from neural regions controlling mesolimbic-dependent regulation of associative opiate reward memory. This review will focus on three of these regions: the basolateral amygdala (BLA), prefrontal cortex (PFC) and ventral hippocampus (vHIPP). Recent evidence demonstrates that all of these regions contain populations of output neurons that target mesolimbic areas including the dopamine (DA) containing neurons of the ventral tegmental area (VTA) and neuronal sub-populations in the nucleus accumbens (NAc). Importantly, signalling through the cannabinoid CB1 receptor (CB1R) system within these circuits has been shown to powerfully regulate the affective and memory-related processing of opiate-dependent motivational signals.