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Title
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Free feeding and intake following regulatory challenges in rats: Roles of selective opioid receptor subtype antagonists.
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Identifier
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AAI9224790
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identifier
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9224790
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Creator
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Arjune, Dulmanie.
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Contributor
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Adviser: Richard J. Bodnar
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Date
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1992
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Physiological
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Abstract
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The present studies evaluated the central effects of the specific antagonists, beta-funaltrexamine ({dollar}\beta{dollar}-FNA), nor-binaltorphimine (Nor-BNI) and (D-Ala{dollar}\sp2{dollar}, Leu{dollar}\sp5{dollar}, Cys{dollar}\sp6{dollar}) -Enkephalin (DALCE), upon ingestive behavior, specifically under such conditions as spontaneous intake, food deprivation, 2DG glucoprivation, palatable intake and nocturnal feeding. {dollar}\beta{dollar}-FNA is a non-equilibrium, long-term antagonist of the mu receptor and a reversible, short-term agonist of the kappa opioid receptor. Nor-BNI is a highly-selective kappa receptor antagonist with a 170-fold greater affinity for kappa relative to mu receptors. DALCE acts as a short-acting delta, and secondarily mu, agonist and as a long-acting antagonist at the delta receptor. In short-term intake tests, food intake was significantly increased by {dollar}\beta{dollar}-FNA (1-20{dollar}\mu{dollar}g, i.c.v.) for up to 6h and by DALCE (10{dollar}\mu{dollar}g, i.c.v.) for up to 10h. Short-term {dollar}\beta{dollar}-FNA hyperphagia was reduced by the kappa antagonist, Nor-BNI, but not by mu antagonism with {dollar}\beta{dollar}-FNA, suggesting kappa receptor involvement. Similarly, short-term DALCE hyperphagia was eliminated by general opiate (naltrexone: NTX) and kappa (Nor-BNI) antagonism, but was minimally affected by mu ({dollar}\beta{dollar}-FNA) and delta (DALCE) antagonism, indicating that the kappa receptor is in the final common path of this response. Whereas long-term {dollar}\beta{dollar}-FNA (10-20{dollar}\mu{dollar}g) treatment significantly inhibited free feeding 24, 48 and 72h following injection, DALCE (40{dollar}\mu{dollar}g) only minimally decreased food intake and body weight gain after 24-96h. The increased intake demonstrated following 24h of food deprivation was significantly suppressed (33-49%) following {dollar}\beta{dollar}-FNA (10-20{dollar}\mu{dollar}g) pretreatment. In contrast, DALCE, administered prior to food deprivation (24h), failed to affect subsequent 24h intake and only sporadically decreased food intake and body weight after 48 and 72h. Nocturnal intake, assessed two hours into the dark cycle, was significantly inhibited by central pretreatment (1h) with Nor-BNI (20{dollar}\mu{dollar}g, 53-54%) and NTX (20{dollar}\mu{dollar}g, 47-60%). Such evidence indicate that the antagonists display differential response in free feeding (NTX = Nor-BNI {dollar}>{dollar} {dollar}\beta{dollar}-FNA {dollar}\gg{dollar} DALCE) and in deprivation-induced feeding (NTX = {dollar}\beta{dollar}-FNA {dollar}>{dollar} Nor-BNI {dollar}\gg{dollar} DALCE). The hyperphagia induced by the anti-metabolic glucose analogue, 2-deoxy-D-glucose, was significantly inhibited by central {dollar}\beta{dollar}-FNA (10-20{dollar}\mu{dollar}g, 75-100%) pretreatment (24h), Nor-BNI (1-20{dollar}\mu{dollar}g, 33-79%) and NTX (20{dollar}\mu{dollar}g, 40-68%). DALCE (10{dollar}\mu{dollar}g) pretreatment (24h), on the other hand, only transiently (2h) decreased glucoprivic intake. Similarly, the short-term hyperphagia observed following exposure to a high-fat diet was significantly attenuated by central Nor-BNI (1-20{dollar}\mu{dollar}g, 33-79%) and NTX (20{dollar}\mu{dollar}g, 47-51%) while significantly potentiated by long-term DALCE (1{dollar}\mu{dollar}g) pretreatment. These data also indicate that the antagonists exhibit differential response to glucoprivic (NTX = {dollar}\beta{dollar}-FNA {dollar}>{dollar} Nor-BNI {dollar}\gg{dollar} DALCE) and palatable (NTX = Nor-BNI {dollar}>{dollar} {dollar}\beta{dollar}-FNA {dollar}\gg{dollar} DALCE) intakes. Essentially, the opioid receptor subtypes are involved in regulating various forms of ingestive behavior, addressing issues pertaining to obesity, regulatory challenges and palatability.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
