How do brain mechanisms create maladaptive attractions? Here intense maladaptive attractions are created in laboratory rats by pairing optogenetic channelrhodopsin (ChR2) stimulation of central nucleus of amygdala (CeA) in rats with encountering either sucrose, cocaine, or a painful shock-delivering object. We find that pairings make the respective rats pursue either sucrose exclusively, or cocaine exclusively, or repeatedly self-inflict shocks. CeA-induced maladaptive attractions, even to the painful shock-rod, recruit mesocorticolimbic incentive-related circuitry. Shock-associated cues also gain positive incentive value and are pursued. Yet the motivational effects of paired CeA stimulation can be reversed to negative valence in a Pavlovian fear learning situation, where CeA ChR2 pairing increases defensive reactions. Finally, CeA ChR2 valence can be switched to neutral by pairing with innocuous stimuli. These results reveal valence plasticity and multiple modes for motivation via mesocorticolimbic circuitry under the control of CeA activation.

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.

Research over the past decades has demonstrated the explanatory power of emotions, feelings, motivations, moods, and other affective processes when trying to understand and predict how we think and behave. In this consensus article, we ask: has the increasingly recognized impact of affective phenomena ushered in a new era, the era of affectivism?