Roles of GABAA receptor α5 subunit on locomotion and working memory in transient forebrain ischemia in mice
- Authors
- Kim D.H.; Kwon H.; Choi J.W.; Shin C.Y.; Cheong J.H.; Park S.J.; Ryu J.H.
- Issue Date
- Aug-2020
- Publisher
- Elsevier Inc.
- Keywords
- Diazepam; Transient forebrain ischemia; Working memory; γ-Aminobutyric acid
- Citation
- Progress in Neuro-Psychopharmacology and Biological Psychiatry, v.102
- Journal Title
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Volume
- 102
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/70915
- DOI
- 10.1016/j.pnpbp.2020.109962
- ISSN
- 0278-5846
- Abstract
- The γ-aminobutyric acid A (GABAA) receptor, which contains a chloride channel, is a typical inhibitory neurotransmitter receptor in the central nervous system. Although the GABAergic neurotransmitter system has been discovered to be involved in various psychological behaviors, such as anxiety, convulsions, and cognitive function, its functional changes under conditions of ischemic pathological situation are still uncovered. In the present study, we attempted to elucidate the functional changes in the GABAergic system after transient forebrain ischemia in mice. A bilateral common carotid artery occlusion for 20 min was used to establish a model of transient forebrain ischemia/reperfusion (tI/R). Delayed treatment with diazepam, a positive allosteric modulator of the GABAA receptor, increased locomotor activity in the open field test and spontaneous alternations in the Y-maze test in tI/R mice, but not in shams. Delayed treatment with diazepam did not alter neuronal death or the number of GABAergic neurons in tI/R mice. However, tI/R induced changes in the protein levels of GABAA receptor subunits in the hippocampus. In particular, the most marked increase in the tI/R group was found in the level of α5 subunit of the GABAA receptor. Similar to delayed treatment with diazepam, delayed treatment with imidazenil, an α5-sensitive benzodiazepine, increased spontaneous alternations in the Y-maze in tI/R mice, whereas zolpidem, an α5-insensitive benzodiazepine, failed to show such effects. These results suggest that tI/R-induced changes in the level of the α5 subunit of the GABAA receptor can alter the function of GABAergic drugs in a mouse model of forebrain ischemia. © 2020 Elsevier Inc.
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