Dopamine D₁ and D₂ receptor subtypes functional regulation in cerebral cortex of unilateral rotenone lesioned Parkinson's rat model: Effect of serotonin, dopamine and norepinephrine

Parkinsonism Relat Disord. 2011 May;17(4):255-9. doi: 10.1016/j.parkreldis.2010.12.018. Epub 2011 Feb 9.

Abstract

Parkinson's disease is a progressive neurodegenerative disorder characterized by selective degeneration of dopaminergic neurons in substantia nigra pars compacta leading to marked reduction of dopamine levels in the cerebral cortex. The present study analysed the effect of serotonin, dopamine and norepinephrine as treatment on rotenone induced Hemi-Parkinson's disease in rats and its role in the regulation of dopamine receptor subtypes in the cerebral cortex of the experimental rats. Unilateral stereotaxic single dose infusions of rotenone were administered to the substantia nigra of adult male Wistar rats. Neurotransmitters--serotonin, dopamine and norepinephrine treatments--were given to rotenone induced Hemi-Parkinson's rats. Scatchard analysis of Dopamine D₁ and D₂ receptor showed a significant increase (p < 0.001) in the cerebral cortex of the Parkinson's rats compared to control. These altered parameters were reversed to near control in the serotonin and norepinephrine treated Parkinson's disease rats and no change was observed in dopamine treated Parkinson's rats. Real-time PCR results confirmed the receptor data. Our results showed serotonin and norepinephrine functionally reversed the dopamine receptors significantly in rotenone induced Hemi-Parkinson's rat. This has clinical significance in the therapeutic management of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects*
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Functional Laterality
  • Male
  • Neurotransmitter Agents / pharmacology*
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rotenone / toxicity
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Uncoupling Agents / toxicity

Substances

  • Neurotransmitter Agents
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Uncoupling Agents
  • Rotenone
  • Serotonin
  • Dopamine
  • Norepinephrine