The active heroin metabolite 6-acetylmorphine has robust reinforcing effects as assessed by self-administration in the rat

Avvisati, Riccardo, Bogen, Inger Lise, Andersen, Jannike M, Vindenes, Vigdis, Mørland, Jørg, Badiani, Aldo and Boix, Fernando (2019) The active heroin metabolite 6-acetylmorphine has robust reinforcing effects as assessed by self-administration in the rat. Neuropharmacology, 150. pp. 192-199. ISSN 0028-3908

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Abstract

Previous studies have suggested that at least some of the behavioral effects of heroin might be mediated by its active metabolite 6-acetylmorphine (6-AM). The aim of the present study was to investigate the reinforcing effects of 6-AM and its role in mediating those of heroin. We used an intravenous self-administration procedure in male Sprague-Dawley rats including four phases: acquisition, extinction, reinstatement of drug-seeking, and re-acquisition. Independent groups of rats readily learned to self-administer equimolar doses (0.135 μmol/kg) of either 6-AM (44.3 μg/kg) or heroin (50 μg/kg). Under a fixed ratio 1 (FR1) schedule of reinforcement, the rate of responding was the same for 6-AM and heroin, but it was significantly higher for 6-AM than for heroin under a FR2 schedule. A non-contingent infusion (‘priming’) of 0.068 μmol/kg of either 6-AM or heroin reinstated non-reinforced drug-seeking (relapse). The rats readily re-acquired self-administration behaviour when given access to one of two doses (0.068 and 0.135 μmol/kg) of 6-AM or heroin. Pretreatment with a specific monoclonal antibody (mAb) against 6-AM blocked the priming effect of 6-AM, and modified the rate of lever-pressing on re-acquisition of 6-AM self-administration in a manner compatible with a shift to the right of the dose-effect curve. The mAb did not affect heroin responding. The present results show that 6-AM possesses reinforcing effects similar to those of heroin. The lack of effect of 6-AM mAb on heroin priming and heroin self-administration calls for further studies to clarify the role of heroin and its metabolites in heroin reward.

Item Type: Article
Keywords: Heroin; 6-acetylmorphine; Self-Administration; Reinforcement
Schools and Departments: School of Psychology > Psychology
Depositing User: Sanjeedah Choudhury
Date Deposited: 08 Jan 2019 15:09
Last Modified: 19 Dec 2019 02:00
URI: http://sro.sussex.ac.uk/id/eprint/81122

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