BDNF signaling in the VTA links the drug-dependent state to drug withdrawal aversions.

Hector Vargas-Perez, Amine Bahi, Mary Rose Bufalino, Ryan Ting-A-Kee, Geith Maal-Bared, Jenny Lam, Ahmed Fahmy, Laura Clarke, Jennifer K Blanchard, Brett R Larsen, Scott Steffensen, Jean-Luc Dreyer, Derek van der Kooy

Index: J. Neurosci. 34(23) , 7899-909, (2014)

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Abstract

Drug administration to avoid unpleasant drug withdrawal symptoms has been hypothesized to be a crucial factor that leads to compulsive drug-taking behavior. However, the neural relationship between the aversive motivational state produced by drug withdrawal and the development of the drug-dependent state still remains elusive. It has been observed that chronic exposure to drugs of abuse increases brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. In particular, BDNF expression is dramatically increased during drug withdrawal, which would suggest a direct connection between the aversive state of withdrawal and BDNF-induced neuronal plasticity. Using lentivirus-mediated gene transfer to locally knock down the expression of the BDNF receptor tropomyosin-receptor-kinase type B in rats and mice, we observed that chronic opiate administration activates BDNF-related neuronal plasticity in the VTA that is necessary for both the establishment of an opiate-dependent state and aversive withdrawal motivation. Our findings highlight the importance of a bivalent, plastic mechanism that drives the negative reinforcement underlying addiction. Copyright © 2014 the authors 0270-6474/14/347899-11$15.00/0.