RT Journal Article
SR Electronic
T1 BDNF Signaling in the VTA Links the Drug-Dependent State to Drug Withdrawal Aversions
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7899
OP 7909
DO 10.1523/JNEUROSCI.3776-13.2014
VO 34
IS 23
A1 Hector Vargas-Perez
A1 Amine Bahi
A1 Mary Rose Bufalino
A1 Ryan Ting-A-Kee
A1 Geith Maal-Bared
A1 Jenny Lam
A1 Ahmed Fahmy
A1 Laura Clarke
A1 Jennifer K. Blanchard
A1 Brett R. Larsen
A1 Scott Steffensen
A1 Jean-Luc Dreyer
A1 Derek van der Kooy
YR 2014
UL http://www.jneurosci.org/content/34/23/7899.abstract
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.