title: Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization.
abstract: BACKGROUND
  The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH).
  
  
  RESULTS
  We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization.
  
  
  CONCLUSIONS
  Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization.
authors: Research Project for Addictive Substances, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors: Wenhua
authors: W
authors: Han
authors: Yukio
authors: Y
authors: Takamatsu
authors: Hideko
authors: H
authors: Yamamoto
authors: Shinya
authors: S
authors: Kasai
authors: Shogo
authors: S
authors: Endo
authors: Tomoaki
authors: T
authors: Shirao
authors: Nobuhiko
authors: N
authors: Kojima
authors: Kazutaka
authors: K
authors: Ikeda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: C497411:Crem protein, mouse; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D051786:Cyclic AMP Response Element Modulator; D008694:Methamphetamine; C033660:preproenkephalin