Faculté des sciences

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

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

In: The Journal of Neuroscience, 2014, vol. 34, no. 23, p. 7899–7909

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... More

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    Summary
    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.