Effects of tipepidine on MK-801-induced cognitive impairment in mice
| Autor: | Ryo Kawahara, Shogo Misumi, Risa Miki, Ikutaro Honda, Ryota Hamasaki, Fumio Soeda, Tetsuya Shirasaki, Kazuo Takahama |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Patch-Clamp Techniques Pharmacology 03 medical and health sciences Mice 0302 clinical medicine Piperidines Dopamine medicine Animals Cognitive Dysfunction G protein-coupled inwardly-rectifying potassium channel Rats Wistar Cognitive impairment Molecular Biology Clozapine business.industry General Neuroscience Dopaminergic Neurons Ventral Tegmental Area Antidepressive Agents Brain disease Rats Ventral tegmental area Antitussive Agents Disease Models Animal 030104 developmental biology medicine.anatomical_structure G Protein-Coupled Inwardly-Rectifying Potassium Channels Schizophrenia Tipepidine Neurology (clinical) Dizocilpine Maleate business 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | Brain research. 1710 |
| ISSN: | 1872-6240 |
| Popis: | We previously reported that centrally acting non-narcotic antitussives, including tipepidine, inhibit G-protein-coupled inwardly rectifying potassium (GIRK) channel-activated currents of neurons. In addition, when administered at a cough suppressant dose, the drugs ameliorated the symptoms of various models of intractable brain disease in rodents. In the current study, we investigated whether tipepidine causes recovery from schizophrenia-like cognitive dysfunction, which was induced by MK-801 (0.2 mg/kg, i.p.) in mice. We also examined the effect of tipepidine and clozapine co-administration on the dysfunction. Moreover, we studied whether clozapine inhibits GIRK channel activated currents in single brain neurons using the patch-clamp technique. Tipepidine elicited recovery from MK-801-induced cognitive impairment in the novel objective recognition test and Y-maze test. Further, co-administration of tipepidine and clozapine, at subthreshold doses of each drug, improved MK-801-induced cognitive impairment in the novel objective recognition test. Clozapine (3 × 10−5 M) had a minor effect on baclofen-induced currents in dopamine neurons of the ventral tegmental area. |
| Databáze: | OpenAIRE |
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