My Mind is Telling Me No, but My Body is Telling Me Yes: Reward Preference Induced by Optogenetic Central Amygdala Stimulation Persists Despite Competitive Physiological Motivation

Drug addiction involves compulsive pursuit of a reward that persists even in the face of adverse consequences. Previous research has established that optogenetic stimulation of the central amygdala (CeA) generates an addiction-like preference for laser-paired reward that persists in the face of external punishment. The present study however aims to examine whether CeA stimulation-induced reward preference is maintained despite internal physiological consequences using sodium depletion and conditioned taste aversion (CTA). To this end, rats infused with light-activated Channelrhodopsin (ChR2) or control virus (EYFP) were trained to press levers for either a sucrose reward paired with CeA laser stimulation, or an unpaired salt pellet. During the sodium depletion experiment, rats developed a strong preference for the sucrose pellet, and were then repeatedly sodium-depleted in order to shift preference towards the salt reward. Here, EYFP rats shifted their behavior while ChR2 rats did not, maintaining a focused preference for the laser-paired reward despite their growing sodium appetite. In the CTA experiment, rats were presented with two novel sugar pellet flavors, one of which was repeatedly paired with the aversive agent lithium chloride. ChR2 and EYFP rats were then given the option to lever press for the aversive reward paired with laser stimulation, or the unpaired alternative flavored reward. Here, EYFP rats demonstrated a stronger avoidance of the aversive pellet and reduction in laser preference compared to ChR2 rats. These results suggest that CeA stimulation produces a powerful compulsion that can overcome intense physiological motivation, which could provide insight into why addicts forego their own health and biological needs to pursue their preferred reward.