NALOXONAZINE, A HIGH-AFFINITY OPIATE RECEPTOR ANTAGONIST: EFFECTS UPON ANALGESIC AND INGESTIVE PROCESSES (PAIN, MU RECEPTOR, MU1).
Item
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Title
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NALOXONAZINE, A HIGH-AFFINITY OPIATE RECEPTOR ANTAGONIST: EFFECTS UPON ANALGESIC AND INGESTIVE PROCESSES (PAIN, MU RECEPTOR, MU1).
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Identifier
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AAI8515661
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identifier
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8515661
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Creator
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SIMONE, DONALD A.
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Contributor
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Richard J. Bodnar
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Date
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1985
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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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One primary method in investigating the involvement of endogenous opioids in such behaviors as analgesia and ingestion is to observe behavioral changes following administration of opiate antagonists. The primary opiate antagonist employed in behavioral pharmacological research has been naloxone. However, naloxone does not compete equally well for all opiate receptor sub-types. Naloxonazine is a long-lasting opiate antagonist which selectively inhibits MU1 binding sites. Morphine analgesia is eliminated by naloxonazine (10 mg/kg) intravenously (iv) administered 24 h prior to the opiate. To examine central effects of this antagonist, the first experiment evaluated the dose-response relationships of intracerebroventricular (icv) administration of naloxonazine upon basal pain thresholds and morphine analgesia. Groups of six male albino Sprague-Dawley rats, matched for baseline tail-flick latencies and jump thresholds, failed to display changes in these measures for up to 24 h following the central (1, 5 or 50 ug, icv) injections. However, central naloxonazine pretreatment displayed dose-dependent and test-dependent effects in reducing or eliminating morphine analgesia 24 h later.;In the second experiment, rats matched for baseline food intake received an iv injection of either naloxonazine (10 mg/kg) or vehicle. Food intake was assessed 24 h later. Pretreatment with naloxonazine significantly reduced free feeding relative to vehicle treatment. In contrast, central naloxonazine pretreatment failed to reduce free feeding over a 24 h period. In a second study, food intake of six groups of rats deprived of food for 24 h, was assessed 2 and 24 h thereafter. Pretreatment with iv naloxonazine, but not naloxone, prior to deprivation, significantly reduced deprivation-induced intake at 2 h following food reinstatement. Naloxone was effective at reducing intake only when administered shortly (5-15 min) before food reintroduction. In contrast, central pretreatment with naloxonazine (50 ug) prior to deprivation, significantly reduced intake at 24 h, but not at 2 h, after food reinstatement. In a third study, three groups of rats received 2-deoxy-D-glucose (2-DG) (400 mg/kg, ip) either 24 h following naloxonazine (10 mg/kg, iv) or vehicle, or immediately following naloxone (10 mg/kg, sc). Food intake was determined at 2 and 4 h following 2-DG administration. Naloxone significantly reduced 2-DG hyperphagia at 2 and 4 h, and naloxonazine potentiated 2-DG hyperphagia at 4 h following 2-DG administration. (Abstract shortened with permission of author.).
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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.
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Program
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Psychology
