title: Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway.
abstract: OBJECTIVE
  The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity.
  
  
  METHODS
  Ethanol was administered to rats in drinking water at concentration of 6% (v/v) for 30 days. Rats were sacrificed on day 10, 20, or 30 during ethanol intake or on withdrawal day 1, 3, or 7 following 30-d ethanol intake. The striata were removed either for electrophysiological recording or for protein immuno-blot analysis. Extracellular recording technique was used to record population spikes (PS) induced by high-frequency stimulation (HFS) in the dorsolateral striatum (DLS).
  
  
  RESULTS
  Corticostriatal long-term depression (LTD) was determined to be dependent upon ERK signaling. Chronic ethanol intake (CEI) attenuated ERK phosphorylation and LTD induction, whereas withdrawal for one day (W1D) potentiated ERK phosphorylation and LTD induction. These results showed that the impact of chronic ethanol intake and withdrawal on corticostriatal synaptic plasticity was associated with ethanol's effect on ERK phosphorylation. In particular, pharmacological inhibition of ERK hyper-phosphorylation by U0126 prevented LTD induction in the DLS and attenuated ethanol withdrawal syndrome as well.
  
  
  CONCLUSIONS
  In rat DLS, chronic ethanol intake and withdrawal altered LTD induction via ERK signaling pathway. Ethanol withdrawal syndrome is mediated, at least partly, by ERK hyper-phosphorylation in the DLS.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Sheng-zhong
authors.initials: SZ
authors.lastname: Cui
authors.forename: Shen-jun
authors.initials: SJ
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Gui-qin
authors.initials: GQ
authors.lastname: Xie
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Xiao-ru
authors.initials: XR
authors.lastname: Yuan
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases