Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions

Kazuo Matsubara, Keiko Shimizu, Manabu Suno, Kento Ogawa, Toshio Awaya, Takehiro Yamada, Toshihiro Noda, Machiko Satomi, Ko ichi Ohtaki, Kaoru Chiba, Yoshikazu Tasaki, Hiroshi Shiono

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their highest concentrations in the frontal cortex, subthalamic nucleus and entopeduncular nucleus as well as the dorsal and median raphe nucleus. There is growing evidence that 5-HT1A receptor agonists have an antidepressant effect in individuals with major depressive disorders. Recent clinical studies suggest that tandospirone, a highly potent and selective 5-HT1A receptor agonist used clinically as an antidepressant in Japan and China, may act as an antiparkinsonian drug. In the present study, we investigated the effect of tandospirone on contralateral rotational behavior in a unilateral hemiparkinsonian rat model produced with 6-hydroxydopamine (6-OHDA). Tandospirone, as well as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), significantly increased contralateral turnings in a dose-dependent manner (0.5-10 mg/kg). Tandospirone also remarkably potentiated the contralateral turning induced by 0.025 mg/kg of apomorphine. Pretreatment with WAY-100635, a 5-HT1A receptor antagonist, almost completely blocked the contralateral turning behavior evoked by tandospirone and 8-OHDPAT, but not that by apomorphine. SCH-23390, a selective dopamine D1 receptor antagonist, did not affect on the tandospirone-induced rotational behavior. These results suggested that tandospirone could act on postsynaptic 5-HT1A receptors and modulate excitatory amino acid pathways in the basal ganglia. Thus, tandospirone could have therapeutic potential for the treatment of Parkinson's disease by modulating neuronal activities of non-dopaminergic pathways.

Original languageEnglish
Pages (from-to)126-133
Number of pages8
JournalBrain Research
Volume1112
Issue number1
DOIs
Publication statusPublished - Sep 27 2006
Externally publishedYes

Keywords

  • 5-HT1A receptor agonist
  • 6-Hydroxydopamine
  • 8-OHDPAT
  • Parkinson disease
  • Rotation behavior
  • Tandospirone
  • WAY-100635

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions'. Together they form a unique fingerprint.

Cite this