Back to Search
Start Over
The role of 6-acetylmorphine in heroin-induced reward and locomotor sensitization in mice.
- Source :
-
Addiction biology [Addict Biol] 2020 Mar; Vol. 25 (2), pp. e12727. Date of Electronic Publication: 2019 Feb 20. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© 2019 Society for the Study of Addiction.)
- Subjects :
- Analgesics, Opioid blood
Analgesics, Opioid pharmacology
Animals
Brain metabolism
Brain physiopathology
Conditioning, Psychological drug effects
Disease Models, Animal
Heroin blood
Male
Mice
Mice, Inbred C57BL
Opioid-Related Disorders blood
Opioid-Related Disorders metabolism
Brain drug effects
Heroin pharmacology
Locomotion drug effects
Morphine Derivatives blood
Opioid-Related Disorders physiopathology
Reward
Subjects
Details
- Language :
- English
- ISSN :
- 1369-1600
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Addiction biology
- Publication Type :
- Academic Journal
- Accession number :
- 30788879
- Full Text :
- https://doi.org/10.1111/adb.12727