Role of Central Amygdala Opioids in Incentive Motivation: Translating Learning into Focused and Amplified 'Wanting'.

Abstract

Wanting a reward like food is different from liking it, and the brain processes these sensations separately. Components of the limbic system mediate both, and here I examined how different neurochemical signals (opioids and cannabinoids) in particular limbic structures [central amygdala (CeA), basolateral amygdala (BLA), and nucleus accumbens (NAc)] process Pavlovian ‘wanting,’ and hedonic ‘liking.’ Experiment 1 examined how CeA activation targets incentive motivational ‘wanting’ upon particular cues (e.g., an extending lever that signals sucrose reward delivery), to make them stronger ‘motivational magnets.’ Microinjecting the drug DAMGO to stimulate µ opioid receptors in CeA of rats enhanced approach and food consummatory behaviors directed at cues. Experiment 2 examined how amygdala mediates cue-induced motivation to obtain rewards themselves (cue-triggered reward ‘wanting’). Opioid activation of CeA, but not BLA enhanced such cue-triggered motivation, integrating Pavlovian and instrumental learning to create sharper bursts of ‘wanting’ for the predicted reward. ‘Wanting’ is distinguishable from ‘liking,’ so Experiment 3 used taste reactivity procedures to examine if amygdala opioid stimulation also altered the hedonic impact of food when it is consumed. Strikingly, opioid stimulation reduced hedonic ‘liking’ reactions to sweetness, even when it enhanced food ‘wanting.’ This points to a specialized role for amygdala opioids in enhancing reward ‘wanting’ focused by learning, but not hedonic ‘liking’ of the same reward. Experiment 3 raised the question of what brain substrates do enhance reward ‘liking’ (and made it important for me to show that I can identify ‘liking’ enhancement when it does occur using the present methodologies). The nucleus accumbens shell is known to process food ‘liking,’ and so in experiment 4, I found that microinjection of the endocannabinoid anandamide within the dorsomedial shell enhances hedonic ‘liking.’ This is the first demonstration of a brain endocannabinoid ‘hotspot’ for stimulation of sensory pleasure. Altogether, these experiments demonstrated that amygdala opioids play a specialized role in amplifying and focusing ‘wanting’ based on prior learning, while nucleus accumbens endocannabinoids amplify hedonic ‘liking.’ These findings expand our knowledge of how the limbic system produces distinct components of reward and motivation, and carries implications for understanding appetitive disorders including addiction and obesity.