Little is known about how brain mechanisms cause positive affective reactions to natural stimuli. This project aims to identify neural circuits in the shell of the nucleus accumbens that are uniquiely capable of causing increased positive affective reactions to the taste of food. Objective behavioral affective reactions, based on the taste reactivity paradigm (taste-elicted reactions of human infants, other primates, and rats [in this study]) will be studied to assess the effect of brain manipulations on affective reactions.Neurochemical receptor identity: We will identify the neurochemical identity of the opioid receptor subtype(s) in nucleus accumbens responsible for causing positive affective reactions to tastes. We will make microinjections of selective opioid agonists into a region of accumbens shell where we've shown morphine enhances positive affective reactions to the taste of sucrose. Then blockade by microinjection selective opioid antagonists will be used to confirm receptor subtype identity. Then opioid effects will be compared to GABA, DA, and glutamate neurotransmitter effects in accumbens. We expect to find that accumbens opioid receptor activation plays a unique role in causing increased positive affective reactions (contributing to increased food intake).Neuroanatomical identity: We will identify the neuroanatomical boundary of the accumbens site that causes increased positive affective reactions with a combination of excitotoxin lesion mapping and microinjection mapping techniques. We expect based on preliminary results that a caudal medial region of the shell of the nuclues accumbens will be the chief site.Circuit interactions: Finally, we will examine the larger neural system in which accumbens is embedded, specifically the role of efferent projections to target structures in positive affective reaction. This will begin to clarify the neural circuits underlying generation of positive affective reactions, which may be involved in human affective disorders that involve specific deficits of positive affect.
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