BDNF-dependent synaptic sensitization in midbrain dopamine neurons after cocaine withdrawal.
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.
Pu
Lu
L
Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.
Liu
Qing-song
QS
Poo
Mu-ming
MM
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000166:cytology*
D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D003042:Cocaine; D004298:Dopamine