Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naive rats.
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to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naïve rat becomes dependent and withdrawn.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 gamma-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.
Vargas-Perez
Hector
H
Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada. vargashector@yahoo.com
Ting-A Kee
Ryan
R
Walton
Christine H
CH
Hansen
D Micah
DM
Razavi
Rozita
R
Clarke
Laura
L
Bufalino
Mary Rose
MR
Allison
David W
DW
Steffensen
Scott C
SC
van der Kooy
Derek
D
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D003213:Conditioning, Psychological; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006556:Heroin Dependence / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009118:Muscimol / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018492:Dopamine Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009118:Muscimol; D009020:Morphine; D005475:Flupenthixol; D004298:Dopamine; D001640:Bicuculline