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 language | English |
|---|---|
| Pages (from-to) | 126-133 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 1112 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Sep 27 2006 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions
AU - Matsubara, Kazuo
AU - Shimizu, Keiko
AU - Suno, Manabu
AU - Ogawa, Kento
AU - Awaya, Toshio
AU - Yamada, Takehiro
AU - Noda, Toshihiro
AU - Satomi, Machiko
AU - Ohtaki, Ko ichi
AU - Chiba, Kaoru
AU - Tasaki, Yoshikazu
AU - Shiono, Hiroshi
PY - 2006/9/27
Y1 - 2006/9/27
N2 - 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.
AB - 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.
KW - 5-HT1A receptor agonist
KW - 6-Hydroxydopamine
KW - 8-OHDPAT
KW - Parkinson disease
KW - Rotation behavior
KW - Tandospirone
KW - WAY-100635
UR - http://www.scopus.com/inward/record.url?scp=33748433364&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748433364&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2006.07.003
DO - 10.1016/j.brainres.2006.07.003
M3 - Article
C2 - 16884702
AN - SCOPUS:33748433364
VL - 1112
SP - 126
EP - 133
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -