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

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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

Fingerprint

Serotonin 5-HT1 Receptor Agonists
Oxidopamine
Movement Disorders
Receptor, Serotonin, 5-HT1A
8-Hydroxy-2-(di-n-propylamino)tetralin
Apomorphine
Antidepressive Agents
Entopeduncular Nucleus
Serotonin 5-HT1 Receptor Antagonists
Antiparkinson Agents
Subthalamic Nucleus
Dopamine D1 Receptors
Excitatory Amino Acids
Dopamine Antagonists
tandospirone
Major Depressive Disorder
Frontal Lobe
Basal Ganglia
Parkinson Disease
China

Keywords

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

ASJC Scopus subject areas

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

Cite this

Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions. / Matsubara, Kazuo; Shimizu, Keiko; Suno, Manabu; Ogawa, Kento; Awaya, Toshio; Yamada, Takehiro; Noda, Toshihiro; Satomi, Machiko; Ohtaki, Ko ichi; Chiba, Kaoru; Tasaki, Yoshikazu; Shiono, Hiroshi.

In: Brain Research, Vol. 1112, No. 1, 27.09.2006, p. 126-133.

Research output: Contribution to journalArticle

Matsubara, K, Shimizu, K, Suno, M, Ogawa, K, Awaya, T, Yamada, T, Noda, T, Satomi, M, Ohtaki, KI, Chiba, K, Tasaki, Y & Shiono, H 2006, 'Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions', Brain Research, vol. 1112, no. 1, pp. 126-133. https://doi.org/10.1016/j.brainres.2006.07.003
Matsubara, Kazuo ; Shimizu, Keiko ; Suno, Manabu ; Ogawa, Kento ; Awaya, Toshio ; Yamada, Takehiro ; Noda, Toshihiro ; Satomi, Machiko ; Ohtaki, Ko ichi ; Chiba, Kaoru ; Tasaki, Yoshikazu ; Shiono, Hiroshi. / Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions. In: Brain Research. 2006 ; Vol. 1112, No. 1. pp. 126-133.
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AU - Suno, Manabu

AU - Ogawa, Kento

AU - Awaya, Toshio

AU - Yamada, Takehiro

AU - Noda, Toshihiro

AU - Satomi, Machiko

AU - Ohtaki, Ko ichi

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AU - Shiono, Hiroshi

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