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.
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- Wu Ying-Liang
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan Department of Physiology,Shenyang Pharmaceutical University,Wenhua Road 103,Shenyang,Liaoning 110015,China
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- Yoshida Masami
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
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- Emoto Hiroyuki
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
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- Ishii Hideo
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
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- Koga Kiminori
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
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- Tanaka Masatoshi
- Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
Bibliographic Information
- Other Title
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- Effects of Acute and Chronic Administration of MCI-225, a New Selective Noradrenaline Reuptake Inhibitor With 5-HT3 Receptor Blocking Action, on Extracellular Noradirenaline Levels in the hHypotahalamus of Stressed Rats
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Abstract
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.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 83 (1), 31-38, 2000
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679262178816
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- NII Article ID
- 10008184293
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DC%2BD3cXjs12ju7w%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 5399694
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- PubMed
- 10887938
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed