The present proposal intends to investigate the nature of opioid receptor subtype involvement in established feeding models related to obesity, regulatory changes and stress. While suppression of feeding following the opiate receptor antagonist, naloxone has been used as evidence implicating the endogenous opioids in food intake, it cannot specify opioid receptor subtype involvement given its short duration of action and its interaction with multiple opioid receptor subtypes. Naloxonazine is a potent and long-lasting opioid receptor antagonist selective for the mu1 binding site which represents a common, high-affinity binding site for both opiates and enkephalins. Recent work has demonstrated that halox-one and naloxonazine produce different effects in some feeding paradigms and similar effects in others, thereby implicating the mu1 site in some, but not all forms of feeding behavior. Further opiate receptor subtype involvement can be implied from studies using beta-FNA, which alkylates mu receptors, ICI 174864, a delta receptor antagonist, MR2266, a putative kappa receptor antagonist and beta-CNA, which alkylates all opiate receptors. The first specific aim will analyze the effectiveness of these anti-agonists upon deprivation-induced feeding across a dose range of systematic and central injections. The second specific aim will investigate the role of mu1 and other sites in long-term models of weight gain and food intake by chronically administering the above antagonists to genetically-chase rats, rats with medial hypothalamic knife cuts and rats with hypothalamic paraventricular lesions. The third specific aim will investigate the role of mu1 and other sites in short-term models of food intake by acutely administering the above antagonists to insulin-treated rats, rats receiving tail-pinch stress, and rats offered palatable foods and liquids.
Showing the most recent 10 out of 40 publications
