DARPP-32 and Akt regulation in ethanol-preferring AA and ethanol-avoiding ANA rats

Neurosci Lett. 2011 Sep 26;503(1):31-6. doi: 10.1016/j.neulet.2011.08.002. Epub 2011 Aug 7.

Abstract

Ethanol and other addictive drugs affect many intracellular phosphorylation and dephosphorylation cascades. These cascades are thought to be highly important in the regulation of neuronal activity. The present experiments characterized the regulation of three key signaling molecules, DARPP-32 (dopamine and cAMP regulated phosphoprotein, 32kDa), Akt kinase and ERK1/2 (extracellular signal-regulated kinase 1 and 2) in ethanol-preferring AA (Alko, alcohol) and ethanol-avoiding ANA (Alko, non-alcohol) rat lines. Radioactive in situ hybridization was used in drug naïve animals and Western blotting after acute ethanol administration in striatum, hippocampus and prefrontal cortex. The mRNA levels of DARPP-32 in striatal areas were higher in ANA rats than in AA rats. There was no difference in the striatal enriched phosphatase (STEP61), the downstream target of DARPP-32 expression between the rat lines. Ethanol (1.5g/kg) increased phosphorylation of DARPP-32 at threonine 34 in both AA and in ANA rats indicating that acute ethanol activates DARPP-32 similarly in these rat lines. The expression of Akt kinase was higher in the CA1 of hippocampus in ANA than in AA rats and acute ethanol activated Akt in hippocampus in ANA but not in AA rats. No significant alterations in the regulation of ERK1/2 were found in either rat line. Our findings suggest that DARPP-32 and Akt are regulated by ethanol and differences in the regulation of these molecules might contribute to the dramatically different ethanol drinking patterns seen in AA and ANA rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / metabolism*
  • Alcohol Drinking / physiopathology
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain / drug effects
  • Brain / metabolism
  • Central Nervous System Depressants / administration & dosage*
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / genetics
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism*
  • Ethanol / administration & dosage*
  • Gene Expression Regulation / drug effects*
  • Male
  • Microdialysis
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Motor Activity / drug effects
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Threonine / metabolism

Substances

  • Central Nervous System Depressants
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • RNA, Messenger
  • Threonine
  • Ethanol
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 3