Quantitative autoradiographic study on receptor regulation in the basal ganglia in rat model of levodopa-induced motor complications

J Huazhong Univ Sci Technolog Med Sci. 2009 Apr;29(2):156-62. doi: 10.1007/s11596-009-0204-3. Epub 2009 Apr 28.

Abstract

In order to study neurotransmitter receptor regulation in the basal ganglia involved in the functional changes underlying levodopa-induced motor complications, quantitative autoradiography was used to observe receptor bindings of dopamine D1 and D2, N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) and amino butyric acid (GABA) in the basal ganglia of rats that had unilateral nigrostriatal lesions and had been chronically treated with levodopa until motor complications developed. The rats were randomly assigned to three groups: normal, denervated and treatment-complicated groups. The results showed that response duration to levodopa became progressively shorter and abnormal involuntary movement (AIM) score was progressively increased during the course of levodopa treatment. Chronic treatment augmented D1 receptors more than denervation, and reduced D2 receptors that were also increased by dopamine denervation. Striatal NMDA receptors were substantially up-regulated in the treatment-complicated group. Levodopa treatment did not change receptors of nigral AMPA, pallidal GABA, and subthalamic GABA, which remained the same as that in denervation group. However, chronic treatment reversed the increase of nigral GABA receptors caused by the lesion. It was concluded that a shortening of response duration and AIM mimicked levodopa-induced motor complications of Parkinson's patients. These data suggested that up-regulation of dopamine D1 and NMDA receptors in the striatum leads to an imbalance of stimulation through the striatal output pathways, which is associated with levodopa-induced motor complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Basal Ganglia / metabolism*
  • Gene Expression Regulation
  • Levodopa / adverse effects*
  • Male
  • Motor Activity / drug effects
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • Levodopa