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to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naïve rat becomes dependent and withdrawn.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 gamma-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bicuculline / pharmacology
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Brain-Derived Neurotrophic Factor / administration & dosage
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism*
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Brain-Derived Neurotrophic Factor / pharmacology*
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Conditioning, Psychological
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Dopamine / physiology
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Dopamine Antagonists / administration & dosage
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Dopamine Antagonists / pharmacology
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Flupenthixol / administration & dosage
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Flupenthixol / pharmacology
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GABA Agonists / pharmacology
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GABA Antagonists / pharmacology
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Heroin Dependence / metabolism
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Male
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Morphine / administration & dosage
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Muscimol / pharmacology
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Opioid-Related Disorders / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptors, GABA-A / metabolism
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Reward*
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Signal Transduction
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Substance Withdrawal Syndrome / metabolism
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Ventral Tegmental Area / drug effects
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Ventral Tegmental Area / metabolism*
Substances
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Brain-Derived Neurotrophic Factor
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Dopamine Antagonists
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GABA Agonists
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GABA Antagonists
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RNA, Messenger
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Receptors, GABA-A
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Muscimol
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Morphine
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Flupenthixol
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Dopamine
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Bicuculline