Molecular biomarkers of addiction in a model of long-term morphine self-administration in mice

• Autorzy: Skupio U. , Sikora M. , Korostynski M. , Wawrzczak-Bargiela A. , Piechota M. , Przewlocki R.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Chronic exposure to opioids induces various adaptations in brain physiology that lead to formation of dependence and addiction. Commonly used approaches for modeling morphine dependence, such as conditioned place preference and morphine self-administration typically last less than two weeks, which is presumably too short to observe long-lasting alterations in the brain that accompany drug addiction. AIM(S): In the present study, we aimed to establish a novel model of long-term morphine self-administration in C57BL/6J mice. Our second goal was to identify molecular biomarkers, specific transcriptional patterns and signs of genetic predispositions to opiate addiction. METHOD(S): We used automated IntelliCage system to observe the animals in groups. The animals in two separate cages were allowed access to morphine or saccharin solutions for 3 months. We tested animals for symptoms of addiction using paradigms like progressive ratio schedule and intermittent access. Gene expression profiles were evaluated in the striatum using whole-genome microarrays and qPCR. RESULTS: The animals drinking morphine showed addiction-related behavioral pattern when compared with control animals. The analysis of molecular changes revealed long-lasting alterations in gene expression profiles between the analyzed groups of animals. Interestingly, correlation analyses between individual gene expression levels and motivation allowed to identify genes (Epha5, Ncam) that possibly indicate predisposition to addiction-like behaviors. CONCLUSIONS: Our model represents a novel approach for investigating both behavioral and molecular mechanisms of addiction. Mice drinking morphine exhibit many of the addiction-like symptoms compared to control animals. Prolonged morphine intake resulted in adaptive processes in the brain that manifested as altered transcriptional sensitivity to opioids. FINANCIAL SUPPORT: Supported by Polish National Science Centre Grant no. 2013/08/A/NZ3/00848.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.63

Twórcy

autor

Skupio U.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland

autor

Sikora M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland

autor

Korostynski M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland

autor

Wawrzczak-Bargiela A.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland

autor

Piechota M.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland

autor

Przewlocki R.

• Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Cracow, Poland