Neuropeptide Y alters sedation through a hypothalamic Y1-mediated mechanism

Authors

  • Philippe Naveilhan,

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesvag 1, S17177 Stockholm, Sweden
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    • *

      P.N. and J.M.C. contributed equally to the work.

  • Josep M. Canals,

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesvag 1, S17177 Stockholm, Sweden
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    • Present address: Department de Biologica Cellular i Anatomia Patologica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Casanova 143, 08036 Barcelona, Spain.

    • *

      P.N. and J.M.C. contributed equally to the work.

  • Antti Valjakka,

    1. Department of Pharmacology and Toxicology, University of Kuopio, POB 1627, SF-70210 Kuopio, Finland
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  • Jukka Vartiainen,

    1. NOKIA Research Center, Tampere, Finland
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  • Ernest Arenas,

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesvag 1, S17177 Stockholm, Sweden
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  • Patrik Ernfors

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheelesvag 1, S17177 Stockholm, Sweden
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: Dr Patrik Ernfors, as above.
E-mail: patrik@cajal.mbb.ki.se.

Abstract

Neuropeptide Y (NPY) has been reported to profoundly influence and regulate brain circuits involved in a number of behaviours, like anxiety, alcohol intake, pain and energy homeostasis. Here we show that NPY increases sedation induced by different types of anaesthetics through interactions with the Y1 receptor. Consistently, in Y1–/– (homozygote knockout) mice NPY does not potentiate the pentobarbital-induced sedation. Similar results were obtained for avertin but not for ketalar- (NMDA antagonist) induced sedation. Local microinjection of NPY exhibited the strongest potentiating effect on pentobarbital-induced sedation in the posterior hypothalamic area and Y1 expression was found in the dorsal-premammillary and medial part of medial mammillary nuclei. These results show that Y1 is essential for NPY-induced enhancement of sedation and place this activity of NPY in the posterior hypothalamic area, a region of the brain previously implicated in the regulation of the wake–sleep cycle.

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