Ventral Tegmental Area BDNF Induces an Opiate-Dependent–Like Reward State in Naïve Rats
Hector Vargas-Perez,1,*
Ryan Ting-A-Kee,2
Christine H. Walton,3
D. Micah Hansen,3
Rozita Razavi,1
Laura Clarke,2
Mary Rose Bufalino,2
David W. Allison,3
Scott C. Steffensen,3
Derek van der Kooy1,2
The neural mechanisms underlying the transition from a drug-nondependent
to a drug-dependent state remain elusive. Chronic exposure to
drugs has been shown to increase brain-derived neurotrophic
factor (BDNF) levels in ventral tegmental area (VTA) neurons.
BDNF infusions into the VTA potentiate several behavioral effects
of drugs, including psychomotor sensitization and cue-induced
drug seeking. We found that a single infusion of BDNF into the
VTA promotes a shift from a dopamine-independent to a dopamine-dependent
opiate reward system, identical to that seen when an opiate-naïve
rat becomes dependent and withdrawn. This shift involves a switch
in the
-aminobutyric acid type A (GABA
A) receptors of VTA GABAergic
neurons, from inhibitory to excitatory signaling.
2 Institute of Medical Science, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
3 Department of Psychology, Brigham Young University, Provo, UT 84602, USA.
* To whom correspondence should be addressed. E-mail: vargashector{at}yahoo.com
