Disruption of positive affect is a problem in anhedonia, dysphoria and other emotional Positive pathologies ranging from depression to addiction to schizophrenia. affective reaction is needed for well-being in normal daily life. To interpret why positive affect goes wrong in emotional disorders it is first necessary to understand how brain systems normally generate positive affective reactions to pleasant events ('liking'). Yet little is known about how brains generate normal 'liking'reactions to rewards. This project will study brain 'hedonic hotspots'(cubic-millimeter sites able to magnify 'liking') that generate positive affective reactions to a prototypical reward, sweetness. The project will study opioid and endocannabinoid hedonic hotspots in the nucleus accumbens and ventral pallidum that underlie hedonic 'liking'reactions and motivational 'wanting'for natural food reward. The project will combine microinjection techniques with procedures for mapping localization of function and measures of natural homologous 'liking'reactions shared by humans and rodents (taste reactivity paradigm). Predictions are that mu opioid and CB1 endocannabinoid mechanisms share same cubic-millimeter hedonic hotspots in medial shell of nucleus accumbens and in ventral pallidum, and that different accumbens-pallidum circuits can mediate 'liking'versus 'wanting'for the same reward. Results should reveal important features of mechanisms within limbic hotspots that enhance hedonic reactions above normal. It will also reveal the normal roles of those same brain mechanisms in generating ordinary levels of positive affect, and in appetite states such as hunger that modulate hedonic impact. Altogether, the results will provide valuable information about the neural systems that generate positive affect for natural reward. Improved understanding of how brains generate positive affect should provide useful insights and eventual improvements in treatment for the disruption of positive affect involved in eating disorders, addiction, depression, schizophrenia and other mood disorders.
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