Effects of Acute and Chronic Administration of MCI-225, a New Selective Noradrenaline Reuptake Inhibitor With 5-HT_3 Receptor Blocking Action, on Extracellular Noradrenaline Levels in the Hypothalamus of Stressed Rats

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Author(s)

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−HT<SUB>3</SUB>−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

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 83(1), 31-38, 2000-05-01

    The Japanese Pharmacological Society

References:  24

Codes

  • NII Article ID (NAID)
    10008184293
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    5399694
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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