Administration of BDNF in the ventral tegmental area produces a switch from a nicotine-non-dependent D1R-mediated motivational state to a nicotine-dependent-like D2R-mediated motivational state.

Autor: Grieder TE; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Yee M; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Vargas-Perez H; The Nierika Intercultural Medicine Institute, Ocuilan, Mexico., Maal-Bared G; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., George S; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Ting-A-Kee R; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., George O; Department of Psychiatry, UCSD School of Medicine, San Diego, California, USA., van der Kooy D; Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2022 Feb; Vol. 55 (3), pp. 714-724. Date of Electronic Publication: 2022 Jan 10.
DOI: 10.1111/ejn.15579
Abstrakt: Brain-derived neurotrophic factor (BDNF) has been implicated in the transition from a non-dependent motivational state to a drug-dependent and drug-withdrawn motivational state. Chronic nicotine can increase BDNF in the rodent brain and is associated with smoking severity in humans; however, it is unknown whether this increased BDNF is linked functionally to the switch from a nicotine-non-dependent to a nicotine-dependent state. We used a place conditioning paradigm to measure the conditioned responses to nicotine, showing that a dose of acute nicotine that non-dependent male mice find aversive is found rewarding in chronic nicotine-treated mice experiencing withdrawal. A single BDNF injection in the ventral tegmental area (in the absence of chronic nicotine treatment) caused mice to behave as if they were nicotine dependent and in withdrawal, switching the neurobiological substrate mediating the conditioned motivational effects from dopamine D1 receptors to D2 receptors. Quantification of gene expression of BDNF and its receptor, tropomyosin-receptor-kinase B (TrkB), revealed an increase in TrkB mRNA but not BDNF mRNA in the VTA in nicotine-dependent and nicotine-withdrawn mice. These results suggest that BDNF signalling in the VTA is a critical neurobiological substrate for the transition to nicotine dependence. The modulation of BDNF signalling may be a promising new pharmacological avenue for the treatment of addictive behaviour.
(© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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