Subchronic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced GABA release in the substantia nigra, pars reticulata

Brain Res. 2006 Dec 6;1123(1):196-200. doi: 10.1016/j.brainres.2006.09.027. Epub 2006 Oct 9.

Abstract

L-DOPA is the most effective pharmacological agent used for the symptomatic treatment of Parkinson's disease but long-term L-DOPA treatment induces involuntary abnormal movements such as dyskinesias. The present study, using in vivo microdialysis, investigated the effects of a single or subchronic administration of L-DOPA to adult rats with a unilateral 6-OHDA lesion of dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr). The results indicate that a challenge injection of L-DOPA (50 mg/kg, i.p.) significantly increases GABA levels in the SNr of rats treated with a daily repeated administration of L-DOPA (50 mg/kg, i.p.). Further statistical analysis between groups also showed that extracellular GABA levels were significantly higher in the subchronic L-DOPA group than in the group receiving only one injection of L-DOPA. These results show that the subchronic administration of L-DOPA results in a sensitization of enhanced extracellular GABA levels in the SNr.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Dopamine / metabolism
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / adverse effects
  • Drug Administration Schedule
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Male
  • Microdialysis
  • Neurons / metabolism
  • Oxidopamine
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • gamma-Aminobutyric Acid / drug effects
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Antiparkinson Agents
  • Dopamine Agents
  • Levodopa
  • gamma-Aminobutyric Acid
  • Oxidopamine
  • Dopamine