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Acute Morphine Effects on Respiratory Activity in Mice with Target Deletion of the Tachykinin 1 Gene (Tac1-/-)

  • Yuri Shvarev
  • Jonas Berner
  • Andras Bilkei-Gorzo
  • Hugo Lagercrantz
  • Ronny Wickström
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)

Abstract

Search for physiological mechanisms which could antagonize the opioid-induced respiratory depression is of important clinical value. In this study, we investigated the acute effects of morphine on respiratory activity in genetically modified newborn (P2) mice with target deletion of the (Tac1 -/-) gene lacking substance P (SP) and neurokinin A (NKA). In vivo, as shown with whole-body flow barometric plethysmography technique, morphine induced significantly attenuated minute ventilation during intermittent hypoxia in control animals. In contrast, knockout mice revealed significant increase in minute ventilation. In vitro, in brainstem preparation, knockout mice demonstrated greater changes in burst frequency during intermittent anoxia challenge. The data suggest that hereditary deficiency in tachykinins, SP and NKA results in more robust hypoxic response in newborn Tac1-/- mice during respiratory depression induced by morphine.

Keywords

Intermittent Hypoxia Burst Frequency Acute Morphine Target Deletion Respiratory Rhythm Generation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This study was supported by grants from Stiftelsen Frimurare Orden, Barnforskningen vid Astrid Lindgrens Barnsjukhus and Swedish Medical Research Council (MFR, 19X-05234-21DK).

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Yuri Shvarev
    • 1
    • 3
  • Jonas Berner
    • 1
  • Andras Bilkei-Gorzo
    • 2
  • Hugo Lagercrantz
    • 1
  • Ronny Wickström
    • 1
  1. 1.Department of Woman and Child HealthKarolinska InstituteStockholmSweden
  2. 2.Department of Molecular NeurobiologyUniversity Hospital BonnBonnGermany
  3. 3.Institute of Cytology and GeneticsSD RASNovosibirskRussia

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