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Microinjection of methysergide into the raphe nucleus attenuated phrenic long-term facilitation in rats

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Abstract

Exposure to acute intermittent hypoxia (AIH) evokes persistent increase in respiratory activity that lasts up to 60 min after hypoxic episodes have ceased. This persistent increase in phrenic nerve activity (PNA) is known as phrenic long-term facilitation (LTF). AIH-induced phrenic LTF in anesthetized rats is serotonin dependant. The present study was performed to determine whether microinjection of methysergide (4 mM, 20 ± 5 nl), a broad spectrum 5-HT receptor antagonist, into the caudal raphe nuclei influences phrenic LTF. Peak integrated PNA and respiratory frequency were recorded at 15, 30, and 60 min after five 3-min episodes of normocapnic hypoxia in urethane-anesthetized, vagotomized, paralyzed and ventilated male Sprague–Dawley rats. In control animals, phrenic nerve amplitude was elevated 66.7 ± 8.6% from baseline 1 h after episodic hypoxia, indicating phrenic LTF. Experimental microinjections of methysergide prior to AIH exposure attenuated phrenic LTF (amplitude increase 2.62 ± 2.9% over baseline). We conclude that methysergide microinjections into the caudal raphe region attenuated phrenic LTF induced by AIH, indicating involvement of 5-HT receptor activation at a supraspinal level.

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Acknowledgments

The authors thank Jelena Baricevic for her technical assistance; professor Ivica Grkovic from the Department of Anatomy, Histology and Embryology, University of Split School of Medicine, for his histological expertise; and Dr. JoAnn A Giaconi (Glaucoma Division, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA, Los Angeles, USA) for the language correction of the manuscript. This work has been supported by the Croatian Ministry of Science, Education and Sport Grants 216-2163166-3342 and 216-2163166-0513.

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Authors and Affiliations

  1. Department of Neuroscience, University of Split School of Medicine, Soltanska 2, 21000, Split, Croatia

    Maja Valic, Renata Pecotic, Ivana Pavlinac & Zoran Dogas

  2. Department of Physiology, University of Split School of Medicine, Split, Croatia

    Zoran Valic

  3. Department of Pharmacology, School of Dentistry, University of Zagreb, Zagreb, Croatia

    Kristina Peros

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  1. Maja Valic
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  2. Renata Pecotic
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  3. Ivana Pavlinac
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  4. Zoran Valic
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  5. Kristina Peros
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  6. Zoran Dogas
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Correspondence to Zoran Dogas.

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Valic, M., Pecotic, R., Pavlinac, I. et al. Microinjection of methysergide into the raphe nucleus attenuated phrenic long-term facilitation in rats. Exp Brain Res 202, 583–589 (2010). https://doi.org/10.1007/s00221-010-2161-2

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  • DOI: https://doi.org/10.1007/s00221-010-2161-2

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