title: Cocaine Withdrawal Reduces Gamma-Aminobutyric Acid-Ergic Transmission and Gephyrin Expression at Medial Prefrontal Cortex in Cocaine-Conditioned Place-Preference Rats, Which Shows Increased Cocaine Seeking.
abstract: OBJECTIVE
  Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats.
  
  
  METHODS
  CPP test, patch clamp, and Western blot analysis are engaged to test this proposal.
  
  
  RESULTS
  Two-week cocaine withdrawal further increased CPP score, as compared to the 24-hour withdrawn group. The amplitude of GABAergic inhibitory postsynaptic currents (IPSCs) was decreased in 2-week-withdrawn mPFC neurons from cocaine-CPP rats, compared to that of saline-CPP rats. Two-week withdrawal did not alter the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) in mPFC in cocaine-CPP rats. Two-week withdrawal increased the ratio of EPSCs/IPSCs (E/I) in the same mPFC neuron in cocaine-CPP rats. In addition, Western blots showed 2-week cocaine-withdrawn down-regulated gephyrin at postsynaptic density (PSD) sites of mPFC.
  
  
  CONCLUSIONS
  We found decreased GABAergic IPSCs and downregulated gephyrin in PSD at mPFC in 2-week cocaine-withdrawn rats that showed increased CPP, suggesting that an increased E/I ratio and neuron excitability in mPFC may associate with a cocaine-seeking tendency. Strategies aimed at GABAergic synapses in mPFC may therapeutically benefit to cocaine addiction treatment.
authors.affiliation: Department of Neurology, Dongfeng Hospital, Hubei University of Medicine, Shiyan, PR China.
authors.forename: Wenqiong
authors.initials: W
authors.lastname: Yang
authors.forename: Hongsheng
authors.initials: H
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Falan
authors.initials: F
authors.lastname: Duan
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Qingzhen
authors.initials: Q
authors.lastname: Zhou
authors.forename: Wanhong
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects; D003213:Conditioning, Psychological / Q000502:physiology*; D058999:Drug-Seeking Behavior / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D059330:GABAergic Neurons / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C073441:gephyrin; D003042:Cocaine