Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats
In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2000 |
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| Erschienen: |
2000 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
Japanese journal of pharmacology - 83(2000), 1 vom: 21. Mai, Seite 31-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Y L [VerfasserIn] |
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| Themen: |
135991-48-9 |
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| Anmerkungen: |
Date Completed 19.10.2000 Date Revised 25.07.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM108122247 |
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| 100 | 1 | |a Wu, Y L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats |
| 264 | 1 | |c 2000 | |
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| 500 | |a Date Completed 19.10.2000 | ||
| 500 | |a Date Revised 25.07.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Adrenergic Uptake Inhibitors |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Receptors, Serotonin |2 NLM | |
| 650 | 7 | |a Receptors, Serotonin, 5-HT3 |2 NLM | |
| 650 | 7 | |a Serotonin Antagonists |2 NLM | |
| 650 | 7 | |a MCI 225 |2 NLM | |
| 650 | 7 | |a 135991-48-9 |2 NLM | |
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| 700 | 1 | |a Yoshida, M |e verfasserin |4 aut | |
| 700 | 1 | |a Emoto, H |e verfasserin |4 aut | |
| 700 | 1 | |a Ishii, H |e verfasserin |4 aut | |
| 700 | 1 | |a Koga, K |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, M |e verfasserin |4 aut | |
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