Endocannabinoid-Enhanced “Liking” in Nucleus Accumbens Shell Hedonic Hotspot Requires Endogenous Opioid Signals

Introduction: Stimulating either endogenous cannabinoids or opioids within a restricted dorsomedial “hedonic hotspot” in nucleus accumbens (NAc) shell enhances hedonic impact, or “liking” reactions to sweet tastes. In this study, we probed within this hotspot the relationship between endocannabinoid and opioid signals in hedonic enhancement. Materials and Methods: Specifically, we asked whether enhancement of sucrose “liking” by intra-NAc microinjections of the endocannabinoid anandamide requires concurrent endogenous opioid signaling. Results: Co-administration of the opioid antagonist naloxone in the same NAc microinjections with anandamide prevented the endocannabinoid from enhancing orofacial “liking” reactions to sucrose. Since intra-NAc hotspot naloxone injection alone failed to affect hedonics, reversal of anandamide-induced “liking” by opioid blockade reveals an interdependence of opioid and cannabinoid signaling in enhancing taste hedonic impact. Conclusions: These results elaborate our understanding of the mechanisms of hedonic processing of food rewards, and may also carry implications more generally for how opioid and cannabinoid drugs interact to generate natural pleasures, or drug-induced euphoria.