Cover Image

Nicotine increases alcohol self-administration in male rats via a [my]-opioid mechanism within the mesolimbic pathway

Background and Purpose Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is p...

Full description

Saved in:
Bibliographic Details
Main Authors: Domi, Esi (Author) , Xu, Li (Author) , Pätz, Marvin (Author) , Nordeman, Anton (Author) , Augier, Gaëlle (Author) , Holm, Lovisa (Author) , Toivainen, Sanne (Author) , Augier, Eric (Author) , Hansson, Anita C. (Author) , Heilig, Markus (Author)
Format: Article (Journal)
Language:English
Published: 10 September 2020
In: British journal of pharmacology
Year: 2020, Volume: 177, Issue: 19, Pages: 4516-4531
ISSN:1476-5381
DOI:10.1111/bph.15210
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/bph.15210
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.15210
Get full text
Author Notes:Esi Domi, Li Xu, Marvin Pätz, Anton Nordeman, Gaëlle Augier, Lovisa Holm, Sanne Toivainen, Eric Augier, Anita C. Hansson, Markus Heilig
Description
Summary:Background and Purpose Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is presently unknown. Here, we examined the contribution of μ and κ-opioid receptors to nicotine-induced escalation of alcohol self-administration in rats. Experimental Approach Chronic nicotine was tested on alcohol self-administration and motivation to obtain alcohol. We then tested the effect of the κ antagonist CERC-501 and the preferential μ receptor antagonist naltrexone on basal and nicotine-escalated alcohol self-administration. To probe μ or κ receptor adaptations, receptor binding and G-protein coupling assays were performed in reward-related brain regions. Finally, dopaminergic activity in response to alcohol was examined, using phosphorylation of DARPP-32 in nucleus accumbens as a biomarker. Key Results Nicotine robustly induced escalation of alcohol self-administration and motivation to obtain alcohol. This was blocked by naltrexone but not by CERC-501. Escalation of alcohol self-administration was associated with decreased DAMGO-stimulated μ receptor signalling in the ventral tegmental area (VTA) and decreased pDARPP-32 in the nucleus accumbens shell in response to alcohol. Conclusions and Implications Collectively, these results suggest that nicotine contributes to escalate alcohol self-administration through a dysregulation of μ receptor activity in the VTA. These data imply that targeting μ rather than κ receptors may be the preferred pharmacotherapeutic approach for the treatment of alcohol use disorder when nicotine use contributes to alcohol consumption.
Item Description:Im Titel ist "My" als griechischer Buchstabe dargestellt
Gesehen am 21.04.2026
Physical Description:Online Resource
ISSN:1476-5381
DOI:10.1111/bph.15210

Similar Items