The alpha7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

Søren Kristensen, Morten Skøtt Thomsen, Henrik H Hansen, Daniel B Timmermann, Anders Hay-Schmidt, Jens D Mikkelsen

24 Citations (Scopus)

Abstract

Nicotinic alpha7 acetylcholine receptors (alpha7 nAChR) have been shown to enhance attentional function and aspects of memory function in experimental models and in man. The protein Arc encoded by the effector immediate early gene arc or arg3.1 has been shown to be strongly implicated in long-term memory function. We have sought to determine if alpha7 nAChR mediate the stimulation of arc gene expression, and if so, where in the brain such activation may occur using semi-quantitative in situ hybridisation. Administration of the novel and selective alpha7 nAChR agonist, SSR180711 (1, 3 and 10 mg/kg) to adolescent rats, produced a dose- and time-dependent increase in the expression of Arc mRNA in the prefrontal cortex and the ventral orbital cortex. By contrast, no change in mRNA levels was detected in the parietal cortex and the CA1 of the hippocampus. These data show that alpha7 nAChR activates a subset of neurons in the rat prefrontal cortex and this activation likely is important for the attentional effects of this new class of drugs.
Original languageEnglish
JournalNeuroscience Letters
Volume418
Issue number2
Pages (from-to)154-8
Number of pages5
ISSN0304-3940
DOIs
Publication statusPublished - 17 May 2007

Keywords

  • Acetylcholine
  • Animals
  • Attention
  • Attention Deficit Disorder with Hyperactivity
  • Bicyclo Compounds, Heterocyclic
  • Cytoskeletal Proteins
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • In Situ Hybridization
  • Male
  • Memory
  • Memory Disorders
  • Nerve Tissue Proteins
  • Nicotinic Agonists
  • Prefrontal Cortex
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic
  • Synaptic Transmission
  • Time Factors
  • Up-Regulation
  • alpha7 Nicotinic Acetylcholine Receptor

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