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The role of 6‐acetylmorphine in heroin‐induced reward and locomotor sensitization in mice
Author(s) -
Kvello Anne Marte Sjursen,
Andersen Jannike Mørch,
Boix Fernando,
Mørland Jørg,
Bogen Inger Lise
Publication year - 2020
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12727
Subject(s) - sensitization , heroin , pharmacology , locomotor activity , conditioned place preference , morphine , psychology , addiction , opioid , drug , medicine , neuroscience , receptor
We have previously demonstrated that heroin's first metabolite, 6‐acetylmorphine (6‐AM), is an important mediator of heroin's acute effects. However, the significance of 6‐AM to the rewarding properties of heroin still remains unknown. The present study therefore aimed to examine the contribution of 6‐AM to heroin‐induced reward and locomotor sensitization. Mice were tested for conditioned place preference (CPP) induced by equimolar doses of heroin or 6‐AM (1.25‐5 μmol/kg). Psychomotor activity was recorded during the CPP conditioning sessions for assessment of drug‐induced locomotor sensitization. The contribution of 6‐AM to heroin reward and locomotor sensitization was further examined by pretreating mice with a 6‐AM specific antibody (anti–6‐AM mAb) 24 hours prior to the CPP procedure. Both heroin and 6‐AM induced CPP in mice, but heroin generated twice as high CPP scores compared with 6‐AM. Locomotor sensitization was expressed after repeated exposure to 2.5 and 5 μmol/kg heroin or 6‐AM, but not after 1.25 μmol/kg, and we found no correlation between the expression of CPP and the magnitude of locomotor sensitization for either opioid. Pretreatment with anti–6‐AM mAb suppressed both heroin‐induced and 6‐AM–induced CPP and locomotor sensitization. These findings provide evidence that 6‐AM is essential for the rewarding and sensitizing properties of heroin; however, heroin caused stronger reward compared with 6‐AM. This may be explained by the higher lipophilicity of heroin, providing more efficient drug transfer to the brain, ensuring rapid increase in the brain 6‐AM concentration.