title: Activation of protein kinase C is required for AMPA receptor GluR1 phosphorylation at serine 845 in the dorsal striatum following repeated cocaine administration.
abstract: BACKGROUND
  Phosphorylation in the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors plays a crucial role in the regulation of AMPA receptor plasticity associated with drugs of abuse.
  
  
  OBJECTIVE
  It is well known that phosphorylation of AMPA receptor GluR1 subunit at serine 845 (S845) is regulated by protein kinase A downstream to dopamine D1 receptors in the striatum. This study was performed to determine whether GluR1-S845 phosphorylation in the rat dorsal striatum is altered by repeated cocaine via a signaling mechanism involving glutamate receptor-associated and Ca(2+)-dependent protein kinases.
  
  
  RESULTS
  Systemic administration of cocaine (20 mg/kg, once a day for 7 days) upregulated GluR1-S845 phosphorylation. This upregulation was mediated via a mechanism involving stimulation of group I metabotropic glutamate receptor 1, N-methyl-D-aspartate receptors, and inositol 1,4,5-triphosphate-sensitive receptors. Interactions of several protein kinases, including protein kinase C, Ca(2+)/calmodulin-dependent protein kinase II, and extracellular signal-regulated kinases, are also involved in this event. Protein phosphatases further control S845 phosphorylation by dephosphorylating S845 and phosphorylated protein kinases.
  
  
  CONCLUSIONS
  These findings suggest that phosphorylation of AMPA receptors at GluR1-S845 is upregulated by interactions of glutamate receptor-coupled Ca(2+)-dependent protein kinases following repeated cocaine administration in the dorsal striatum.
authors: Department of Biological Sciences, Pusan National University, Pusan 609-735, South Korea.
authors: Jeong Hwan
authors: JH
authors: Oh
authors: Ju Hwan
authors: JH
authors: Yang
authors: Sung Min
authors: SM
authors: Ahn
authors: BuHyun
authors: B
authors: Youn
authors: Byung-Tae
authors: BT
authors: Choi
authors: John Q
authors: JQ
authors: Wang
authors: Eun Sang
authors: ES
authors: Choe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D003042:Cocaine; D011493:Protein Kinase C; D021122:Protein Subunits; D018091:Receptors, AMPA; D012694:Serine