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
  • Yoshida Masami
    Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
  • Emoto Hiroyuki
    Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
  • Ishii Hideo
    Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
  • Koga Kiminori
    Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan
  • Tanaka Masatoshi
    Department of Pharmacology,Kurume University School of Medicine,Asahi-Machi 67,Kurume 830-0011,Japan

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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.

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