title: The serotonin 5-HT₁A receptor agonist tandospirone improves executive function in common marmosets.
abstract: Previous pilot clinical studies have shown that the serotonin 5-HT1A 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 (0.3mg/kg) and haloperidol (0.3mg/kg) decreased the number of correct responses in this trial. On the other hand, blonanserin (0.1-0.3mg/kg), an atypical antipsychotic highly selective for dopamine D2/D3 and serotonin 5-HT2A receptors, did not affect the number of correct responses in both the easy and difficult trials. Co-treatment with tandospirone (20mg/kg) and risperidone (0.1-0.3mg/kg) or haloperidol (0.1-0.3mg/kg) did not improve animals' performance in the difficult trial. However, co-treatment with tandospirone and blonanserin (0.1-0.3mg/kg) increased the number of correct responses in the difficult trial. In addition, treatment with the dopamine D1 receptor agonist SKF-81297 at 1mg/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-HT1A receptor.
authors: Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Satoko
authors: S
authors: Baba
authors: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Takeshi
authors: T
authors: Murai
authors: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Tomokazu
authors: T
authors: Nakako
authors: Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Takeshi
authors: T
authors: Enomoto
authors: Innovative Drug Discovery Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Michiko
authors: M
authors: Ono
authors: Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan.
authors: Isao
authors: I
authors: Shimizu
authors: Ikeda Lab., Drug Development Research Laboratories, Sumitomo Dainippon Pharma, Co., Ltd., Osaka, Japan. Electronic address: kazuhito-ikeda@ds-pharma.co.jp.
authors: Kazuhito
authors: K
authors: Ikeda
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002144:Callithrix; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D056344:Executive Function / Q000187:drug effects* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011581:Psychological Tests; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D054833:Isoindoles; D010879:Piperazines; D010880:Piperidines; D011619:Psychotropic Drugs; D011743:Pyrimidines; D017447:Receptors, Dopamine D1; D058825:Serotonin 5-HT1 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C055267:tandospirone; C079310:blonanserin; D006220:Haloperidol; D018967:Risperidone
keywords: Antipsychotic; Common marmoset; Executive function; Object retrieval with detour; Schizophrenia; Serotonin 5-HT1A receptor