The proposal hypothesizes that neuroadaptations in CRF systems ofthe extended amygdala mediate negative affective consequences of palatable food withdrawal and thereby come to compel palatable food intake via a negative reinforcement mechanism. Studies use a novel animal model based on """"""""intermittent, but extended, access to palatable food that shares conceptual underpinnings with drug dependence-models and which emphasizes the """"""""dark side"""""""" of food addiction, an understudied, innovative area of research. Preliminary studies with the model found that consummatory and affective dependence on palatable food develop with intermittent access and suggest that palatable food may come to be eaten compulsively for acquired negative reinforcing properties, as has been proposed for abused drugs. In addition, behavioral, molecular and electrophysiological preliminary studies, generated by the applicant during the K99 pahse ofthe award, suggest a key role for CRFl receptor in the alterations observed during withdrawal from preferred food in this model.
Specific Aims 1 and 2 combine sophisticated behavioral techniques (progressive ratio reinforcement schedules, intracranial selfstimulation, elevated plus maze) with complementary neuropharmacologic and brain site-specific lentiviral siRNA knockdown approaches to determine the role of CRFl receptors in the hypophagia, motivational deficits, and anxiogenic-like behavior that is seen upon withdrawal from palatable food.
Specific Aim 3 identifies molecular changes in mRNA and protein expression of CRF/CRFl systems in discrete regions ofthe central extended amygdala that are observed during withdrawal from chronic, intermittent palatable food access.
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