Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 55, Issue 3, Pages 714-724Publisher
WILEY
DOI: 10.1111/ejn.15579
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Funding
- Consejo de Investigacion Sobre Salud y Cerveza de Mexico A. C
- Canadian Institutes of Health Research
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Brain-derived neurotrophic factor (BDNF) plays a crucial role in the transition from a non-dependent motivational state to a drug-dependent and drug-withdrawn motivational state. Chronic nicotine increases BDNF in the rodent brain and is associated with smoking severity in humans. The signaling of BDNF in the ventral tegmental area (VTA) is identified as a critical neurobiological substrate for the transition to nicotine dependence.
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(BDNF) has been implicated in the transition from a non-dependent motivational state to a drug-dependent and drug-withdrawn motivational state.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B (TrkB), revealed an increase in TrkB mRNA but not BDNF mRNA in the VTA in nicotine-dependent and nicotine-withdrawn mice.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.
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