Changes in the mRNA levels of α2A and α2C adrenergic receptors in rat models of Parkinson's disease and L-DOPA-induced dyskinesia

J Mol Neurosci. 2012 Jan;46(1):145-52. doi: 10.1007/s12031-011-9539-x. Epub 2011 May 12.

Abstract

The changes in the mRNA levels of α(2A) and α(2C) adrenoceptors were investigated in unilateral 6-OHDA-lesioned rat model of Parkinson's disease and L: -DOPA-induced dyskinesia using in situ hybridization. In the untreated 6-OHDA-lesioned rats, α(2A) expression was elevated in the locus coeruleus (160 ± 8% and 142 ± 8% in lesioned and unlesioned sides compared to the comparable side in sham-operated rats). Following long-term (21 days, twice daily) treatment with L: -DOPA (25 mg/kg L: -DOPA methyl ester plus benserazide 6.25 mg/kg) in 6-OHDA-lesioned rats, levels of α(2A) adrenoceptor mRNA in the locus coeruleus were decreased, compared to the 6-OHDA-lesioned rats, returning to the levels of α(2A) mRNA in the sham-operated rats. α(2A) adrenoceptor expression was not changed in other brain regions in any treatment group. There was no change in α(2C) expression in the rostral or caudal striatum in which the highest density of α(2C) mRNA is present. In conclusion, the data presented in this study demonstrate an increase in α(2A) adrenoceptor mRNA in the locus coeruleus in the 6-OHDA-lesioned rat model of Parkinson's disease. In addition, the data show that repeated treatment with L: -DOPA in 6-OHDA-lesioned rats, which induces dyskinesia, restores α(2A) mRNA levels. These changes of α(2A) mRNA expression, observed in the locus coeruleus, might be of importance to basal ganglia transmission and motor function.

MeSH terms

  • Adrenergic Agents / toxicity
  • Animals
  • Antiparkinson Agents / adverse effects
  • Basal Ganglia / metabolism
  • Basal Ganglia / physiology
  • Corpus Striatum / physiology
  • Disease Models, Animal
  • Dyskinesia, Drug-Induced / genetics
  • Dyskinesia, Drug-Induced / physiopathology*
  • Levodopa / adverse effects*
  • Locus Coeruleus / physiology
  • Male
  • Motor Activity / physiology
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / physiopathology*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-2 / genetics*

Substances

  • Adra2a protein, rat
  • Adrenergic Agents
  • Antiparkinson Agents
  • RNA, Messenger
  • Receptors, Adrenergic, alpha-2
  • Levodopa
  • Oxidopamine