Deletion of GIRK2 subunit containing GIRK channels of neurons expressing dopamine transporter decrease immobility time on forced swimming in mice
| Autor: | Kimi Araki, Min Chul Shin, Shogo Misumi, Fumio Soeda, Ken Ichi Yamamura, Ikutaro Honda, Sokichi Honda, Kazuo Takahama |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Mice Transgenic Inhibitory postsynaptic potential Open field 03 medical and health sciences 0302 clinical medicine Dopamine receptor D1 Dopamine Internal medicine medicine Animals G protein-coupled inwardly-rectifying potassium channel Swimming Dopamine transporter Depressive Disorder biology Chemistry Dopaminergic Neurons General Neuroscience Ventral Tegmental Area Antidepressive Agents Ventral tegmental area Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology G Protein-Coupled Inwardly-Rectifying Potassium Channels biology.protein Dopamine Antagonists Tipepidine 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience Letters. 665:140-146 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2017.11.028 |
| Popis: | We previously reported that non-narcotic antitussives possessing inhibitory actions on G protein-coupled inwardly rectifying potassium (GIRK) channels have antidepressant-like effects in the forced swimming test in normal and adrenocoticotropic hormone (ACTH) treated rats. Furthermore, the antidepressant-like effects of the antitussives such as tipepidine were blocked by dopamine D1 receptor antagonist, and inhibitory actions on GIRK channels of dopamine neurons may be involved in the antidepressant-like effects of tipepidine. In this study, we generated GIRK2DATKO mice with Girk2/Kcnj6 conditional deletion and assessed depression-related behavior of the mice. The Cre/loxP system was used to selectively delete GIRK2 subunit containing GIRK channels in the neurons expressing dopamine transporter. First, deletion of GIRK2 subunits in the ventral tegmental area (VTA) neurons expressing dopamine transporters was confirmed by hisitochemically and electrophysiologically. In the mice, a significant decrease in the immobility time of forced swimming test was observed. Locomotor activity of the mice was not changed compared to that of GIRK2floxed mice, when tested in the open field. These results suggest that the antidepressant-like effect of antitussives such as tipepidine may be caused partly through the inhibitory actions on GIRK channels in the dopamine neurons. |
| Databáze: | OpenAIRE |
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