The Ventral Pallidum as a Limbic Pleasure Generator.

Abstract

There are three questions that I propose to answer in this dissertation in order to elucidate the role of the ventral pallidum in hedonic ‘liking’ processes, or pleasure generation. The first question is where in the ventral pallidum (VP) or adjacent region does neural dysfunction eliminate positive ‘liking’ and instead cause aversive ‘disliking’ and loss of reward even for sucrose taste. The goal is to identify the specific ‘disliking’ site in VP, where loss of function causes aversion to sweet reward. I found a 0.8 mm3 aversive site in the caudal VP where GABA inhibition or lesion suppressed hedonic ‘liking’ reactions to a sweet taste and replace them with aversive ‘disliking’ reactions (along with loss of food appetite). The second question is to compare and contrast the VP and the NAc shell (NAcSh) regarding whether their hedonic hotspots are necessary for normal positive ‘liking’ reactions. This question asks whether each hotspot is both necessary (for normal ‘liking’) and sufficient (able to enhance ‘liking’ above normal). I found that the caudal VP is the only site that is both necessary (for normal ‘liking’) and sufficient (able to enhance ‘liking’ above normal) for ‘liking’ of a sweet taste. In comparison, the NAcSh, though widely recognized for its role in reward, is only sufficient for ‘liking’ enhancement but not necessary for the maintenance of normal ‘liking’. The third goal is to identify other neurotransmitters in the VP that can amplify ‘liking’ reactions. Before this dissertation, only microinjections of DAMGO, u-opioid agonist, in the posterior VP cause increased of hedonic ‘liking’ reactions. I identify two other neurotransmitters that intensely enhanced ‘liking’: orexin and anandamide. Both the orexin hedonic hotspot and the anandamide hotspot are located in the posterior VP at a site that highly overlaps with the opioid hedonic hotspot. Overall, the findings of the dissertation suggest that VP is actively involved in pleasure generation in the brain, and the malfunction of VP leads to loss of pleasure. The results have broader implications on human reward processes and related clinical disorders, such as depression, addictions, and obesity.