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Lentiviral-mediated up-regulation of let-7d microRNA decreases alcohol intake through down-regulating the dopamine D3 receptor

  • Bahi, Amine College of Medicine, Ajman University, Ajman, UAE - Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, UAE
  • Dreyer, Jean-Luc Division of Biochemistry, Department of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland
    01.08.2020
Published in:
  • European Neuropsychopharmacology. - 2020, vol. 37, p. 70–81
English Recent studies have shown that Lethal-7 (let-7) microRNA (miRNA) is involved in a wide range of psychiatric disorders such as anxiety, depression, schizophrenia, and cocaine addiction. However, the exact role of let-7d miRNA in regulating ethanol intake and preference remains to be elucidated. The aim of the present study was to clarify the role of accumbal let-7d in controlling ethanol-related behaviors in adult rats. For this purpose, stereotaxic injections of let-7d-overexpressing lentiviral vectors (LV) were administered bilaterally into the nucleus accumbens (Nacc) of Wistar rats. The ethanol-related behaviors were investigated using the two-bottle choice (TBC) access paradigm, in which the rats had access to 2.5, 5, and 10% ethanol solutions, the grid hanging test (GHT) and ethanol-induced loss-of-righting-reflex (LORR) test. The results showed that intra-accumbally administered let-7d-overexpressing LV significantly decreased ethanol intake and preference without having significant effects on body weight, consumption or preference for tastants (saccharin and quinine) or ethanol metabolism. Furthermore, accumbal let-7d increased resistance to ethanol-induced sedation in the GHT and LORR test. Most importantly, the data showed that the dopamine D3 receptor (D3R) was a candidate target of let-7d In fact, and using real time PCR, let-7d was found to directly target D3R mRNA to decrease its expression. Further analyses proved that D3R expression was negatively correlated with the levels of let-7d and ethanol-related behaviors parameters. Taken together, the data indicating that let-7d impaired ethanol-related behaviors by targeting D3R will open up new exciting possibilities and might provide potential therapeutic evidence for alcoholism.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/308914
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