Abstract
The neural mechanism underlying the relapse to drug use after drug withdrawal is largely unknown. We found that after withdrawal from repeated cocaine exposure, excitatory synapses onto dopamine neurons in the ventral tegmental area (VTA) of the rat midbrain became highly susceptible to potentiation by weak presynaptic stimuli, an effect requiring endogenous brain-derived neurotrophic factor-tyrosine kinase B (BDNF-TrkB) signaling. The elevated BDNF expression in the VTA after cocaine withdrawal may prime these synapses for potentiation by cue-associated activity, triggering drug craving and relapse.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Animals, Newborn
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Behavior, Animal
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Brain-Derived Neurotrophic Factor / metabolism*
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Cocaine / administration & dosage
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Dopamine / metabolism*
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Dopamine Uptake Inhibitors / administration & dosage
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Electric Stimulation / methods
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay / methods
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / radiation effects
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Gene Expression Regulation / drug effects
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In Vitro Techniques
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Patch-Clamp Techniques / methods
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Rats
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Rats, Sprague-Dawley
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Substance Withdrawal Syndrome / etiology
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Substance Withdrawal Syndrome / physiopathology*
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Synapses / drug effects*
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Ventral Tegmental Area / cytology*
Substances
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Brain-Derived Neurotrophic Factor
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Dopamine Uptake Inhibitors
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Enzyme Inhibitors
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Cocaine
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Dopamine