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 Kooy^1,2

Abstract: 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to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naïve rat becomes dependent and withdrawn.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.

¹ Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
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

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