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

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posted on 2023-06-09, 16:24 authored by Riccardo Avvisati, Inger Lise Bogen, Jannike M Andersen, Vigdis Vindenes, Jørg Mørland, Aldo Badiani, Fernando Boix
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Neuropharmacology

ISSN

0028-3908

Publisher

Elsevier

Volume

150

Page range

192-199

Department affiliated with

  • Psychology Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-01-08

First Open Access (FOA) Date

2019-12-19

First Compliant Deposit (FCD) Date

2019-01-03

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