Differential regulation of AP-1 DNA-binding activity by D1 and D2 dopamine receptor antagonists in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle

Kenichi Kashihara, Kazuhumi Akiyama, Takeshi Ishihara, Yasuhiro Manabe, Koji Abe

Research output: Contribution to journalArticle

Abstract

The effect of D1 and D2 dopamine receptor antagonists on the DNA- binding activity of the AP-1 transcription factor was studied in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle. In the caudate-putamen, vehicle-treated rats showed increased AP-1 DNA-binding activity, which appeared to be reversed completely by treatment with the D1 receptor antagonist SCH23390 (1 mg kg- 1 i.p.) and partially by the D2 antagonist sulpiride (50 mg kg-1 i.p.). In the globus pallidus, vehicle and sulpiride did not induce AP-1, while SCH23390 increased it significantly. This induction was much more prominent in the 6-OHDA-lesioned hemisphere than in the intact hemisphere. The present study suggests that in the caudate-putamen, dopamine-depletion induces long- lasting enhancement of AP-1 DNA-binding activity via activation of D1 receptors and the simultaneous activation of D2 receptors facilitate it. However, in the globus pallidus of the 6-OHDA-lesioned hemisphere, D1 but not D2 antagonism induces AP-1 in certain cell populations which may be distinct from those expressing AP-1 upon stimulation of D2 receptors.

Original languageEnglish
Pages (from-to)175-179
Number of pages5
JournalNeurological Research
Volume21
Issue number2
DOIs
Publication statusPublished - Jan 1 1999

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Keywords

  • AP-1
  • Caudate-putamen
  • Dopamine antagonist
  • Globus pallidus
  • SCH23390
  • Sulpiride

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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