Nov 2, 2018

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

Abstract

Background and Purpose: The 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 Approach: Male 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 Results: Rats 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 wa...Continue Reading

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Mentioned in this Paper

Prescription Procedure
Study
HMGN2P12
Drug Usage
Brain
Withdrawal (Dysfunction)
Oxycodone Measurement
GLS2
Pharmacologic Substance
Intracranial

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