BDNF signaling in the VTA links the drug-dependent state to drug withdrawal aversions.
Research paper by
Hector H Vargas-Perez, Amine A Bahi, Mary Rose MR Bufalino, Ryan R Ting-A-Kee, Geith G Maal-Bared, Jenny J Lam, Ahmed A Fahmy, Laura L Clarke, Jennifer K JK Blanchard, Brett R BR Larsen, Scott S Steffensen, Jean-Luc JL Dreyer, Derek D van der Kooy
6th Jun 2014
6th Jun 2014
The Journal of neuroscience : the official journal of the Society for Neuroscience
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.