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The serotonin 5-HT1A receptor agonist tandospirone improves executive function in common marmosets

Published on Jul 1, 2015in Bioorganic & Medicinal Chemistry Letters2.45
· DOI :10.1016/j.bbr.2015.03.025
Satoko Baba2
Estimated H-index: 2
,
Takeshi Murai5
Estimated H-index: 5
+ 4 AuthorsKazuhito Ikeda6
Estimated H-index: 6
Abstract
Abstract Previous pilot clinical studies have shown that the serotonin 5-HT 1A receptor agonist tandospirone has beneficial effect on cognitive deficits associated with schizophrenia. In the present study, we evaluated the cognitive efficacy of tandospirone, given alone or in combination with the antipsychotic blonanserin, risperidone or haloperidol, on executive function in marmosets using the object retrieval with detour (ORD) task. Treatment with tandospirone alone at 20 and 40 mg/kg increased the number of correct responses in the difficult trial, while risperidone (0.3 mg/kg) and haloperidol (0.3 mg/kg) decreased the number of correct responses in this trial. On the other hand, blonanserin (0.1–0.3 mg/kg), an atypical antipsychotic highly selective for dopamine D 2 /D 3 and serotonin 5-HT 2A receptors, did not affect the number of correct responses in both the easy and difficult trials. Co-treatment with tandospirone (20 mg/kg) and risperidone (0.1–0.3 mg/kg) or haloperidol (0.1–0.3 mg/kg) did not improve animals’ performance in the difficult trial. However, co-treatment with tandospirone and blonanserin (0.1–0.3 mg/kg) increased the number of correct responses in the difficult trial. In addition, treatment with the dopamine D 1 receptor agonist SKF-81297 at 1 mg/kg increased marmosets correct responses in the difficult trial. These results suggest that tandospirone is a promising candidate for the treatment of cognitive deficits associated with schizophrenia and that adjunctive treatment with tandospirone and blonanserin is more appropriate for cognitive deficits than combination therapy with tandospirone and risperidone or haloperidol. The results of this study also indicate that the putative mechanism of action of tandospirone might be related to enhancement of dopamine neurotransmission via activation of the 5-HT 1A receptor.
  • References (24)
  • Citations (10)
References24
Newest
#1Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 5
#2Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
Last.Mutsuo Taiji (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 24
view all 6 authors...
#1Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
#2Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 5
Last.Kazuhito Ikeda (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
view all 6 authors...
#1Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 5
#2Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
Last.Kazuhito Ikeda (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
view all 6 authors...
#1Seiya Miyamoto (St. Marianna University School of Medicine)H-Index: 5
#2Nobumi Miyake (St. Marianna University School of Medicine)H-Index: 6
Last.Jeffrey A. Lieberman (Columbia University)H-Index: 81
view all 5 authors...
Cited By10
Newest
#1Wei Zheng (Guangzhou Medical University)H-Index: 105
#2Xiao-Hong Li (Capital Medical University)H-Index: 4
Last.Yu-Tao Xiang (UM: University of Macau)H-Index: 28
view all 8 authors...
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