Previous research suggests that brain opioid activity is triggered by palatable food taste and sustains feeding behavior by mediating incentive-reward. Research also suggests that food deprivation triggers opioid activity that sensitizes the incentive-reward system's response to food taste and other external stimuli. This facilitation of incentive-reward in food-deprived animals is demonstrable as a naloxone-reversible increase in the reinforcing effect of food, electrical brain stimulation, and drugs of abuse.
The aim of the proposed research is to identify the opioid mechanism(s) -in terms of peptide, receptor type, and brain region- that mediates feeding and the potentiation of reward by food deprivation. To achieve this aim, classical electrical brain stimulation paradigms will be utilized. To investigate the involvement of multiple opioid receptor types in feeding, receptor-selective antagonists will be infused into the lateral ventricle and effects on brain stimulation threshold for eliciting feeding will be determined. To investigate the involvement of multiple opioid receptor types in the potentiation of reward by food deprivation, receptor-selective antagonists will be infused into the lateral ventricle and effects on thresholds for self-stimulation reward will be determined in rats that have chronic restricted access to food. To determine whether the potentiation of reward by food deprivation results from opioid receptor upregulation, in vitro autoradiography will be used to analyze multiple opioid receptor binding in brain regions of rats that have had chronic restricted access to food. To determine whether the potentiation of reward by food deprivation results from an increase in basal or stimulated release of opioid peptides, radioimmunoassays and mRNA blot analyses will be used to investigate brain regional changes in opioid peptide utilization in self-stimulating rats that have had chronic restricted access to food. Any region-specific change in the opioid system of food deprived rats identified in these studies will be subject to follow-up study using local microinjections of receptor-selective opioid agonists, antagonists, and antibodies to opioid peptides. Effects of these microinjections on thresholds for eliciting feeding and self-stimulation will be determined. Finally, any opioid mechanism found to regulate brain stimulation-induced feeding or reward will be investigated in further microinjection studies for a role in """"""""natural' feeding behavior driven by palatability, deprivation, or circadian factors. Since the neural system that mediates the reinforcement of feeding is also believed to mediate the reinforcing effects of abused drugs, the proposed studies may not only shed light on physiological factors that control the propensity to ingest food but also the propensity to abuse drugs.
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