DOI: 10.1101/460048Nov 17, 2019Paper

Paradoxical changes in brain reward status during opioid self-administration in a novel test of the negative reinforcement hypothesis

BioRxiv : the Preprint Server for Biology
Jacques D. NguyenMichael A Taffe


Background and PurposeThe extra-medical use and addiction of prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models. Experimental ApproachMale Wistar rats were given access to oxycodone IVSA (0.15 mg/kg/infusion, i.v.) in Short Access (ShA; 1 h) or Long Access (LgA; 12 h) sessions for 5 sessions/week followed by intermittent 60 h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. A separate group was first trained in the ICSS procedure and then in oxycodone IVSA in 11 h LgA sessions. Key ResultsRats given LgA to oxycodone escalated their responding more than ShA rats, with significant increases following 60 h discontinuations. Pre-session brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1 h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, p...Continue Reading


Nov 28, 2020·Cellular and Molecular Neurobiology·Cherkaouia KibalyCatherine M Cahill

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