This competitive renewal examines the involvement of opioid receptor subtypes on ingestive behaviors related to issues of obesity, appetite control, regulatory challenges and palatability. Inhibition of ingestive behavior in rats by general opiate receptor antagonists failed to specify the subtypes involved. Specific antagonists of the mu (beta- funaltrexamine; B-FNA), mu1 (naloxonazine), kappa (nor-binaltor-phamine; Nor-BNI) and delta ([D-Ala2, Leu5, Cys6]-enkephalin (DALCE); naltrindole) opioid receptor subtypes were employed in the original grant. The rank- order potencies of inhibition of intake by opioid receptor subtype antagonists are: a) free feeding (general = kappa is greater than mu = mu1 which is much greater than delta); b) deprivation feeding (general = mu = mu1 which is greater than kappa which is much greater than delta); c) 2- deoxy-D-glucose hyperphagia (mu2 greater than general = kappa which is much greater than delta which is greater than mu1); d) insulin hyperphagia (mu2 is much greater than general which is greater than kappa = delta = mu1); e) high-fat intake (kappa is greater than general which is greater than mu2 that is greater than delta which is greater than mu1); f) sucrose intake (general = kappa which is greater than mu2 which is greater than delta = mu1) and g) water deprivation intake (general is greater than mu2 which is greater than kappa which is much greater than delta = mu1). This competitive renewal will evaluate the effects of B-FNA, naloxonazine, Nor- BNI, DALCE, naltrindole and naltrexone upon macronutrient selection, overall ingestive inputs and outputs in a metabolic cage, body temperature and locomotor activity as well as intake in sham feeding rats. The differential roles of multiple kappa receptor subtype agonists - U50, 488H (K1) and naloxone benzoylhydrazone (K3) - will be evaluated for their central stimulatory effects upon deprivation, glucoprivic and palatable intake. The above opioid receptor subtype antagonists will be evaluated for effects upon saline drinking in normal rats, and for fluid intake in rats challenged with either angiotensin II or hypertonic saline. Finally, the chronic effects of long-acting opioid receptor subtype antagonists will be evaluated for changes in intake and body weight in normal, genetically- obese or dietary-obese rats exposed to normal or palatable diets.
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