PT  - JOURNAL ARTICLE
AU  - Vargas-Perez, Hector
AU  - Bahi, Amine
AU  - Bufalino, Mary Rose
AU  - Ting-A-Kee, Ryan
AU  - Maal-Bared, Geith
AU  - Lam, Jenny
AU  - Fahmy, Ahmed
AU  - Clarke, Laura
AU  - Blanchard, Jennifer K.
AU  - Larsen, Brett R.
AU  - Steffensen, Scott
AU  - Dreyer, Jean-Luc
AU  - van der Kooy, Derek
TI  - BDNF Signaling in the VTA Links the Drug-Dependent State to Drug Withdrawal Aversions
AID  - 10.1523/JNEUROSCI.3776-13.2014
DP  - 2014 Jun 04
TA  - The Journal of Neuroscience
PG  - 7899--7909
VI  - 34
IP  - 23
4099  - http://www.jneurosci.org/content/34/23/7899.short
4100  - http://www.jneurosci.org/content/34/23/7899.full
SO  - J. Neurosci.2014 Jun 04; 34
AB  - 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.