Opioids modulate cell division in the germinal zone of the late embryonic neocortex

Authors

  • Kyrill Reznikov,

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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  • 1 Kurt F. Hauser,

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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  • 2 Galina Nazarevskaja,

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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  • 3 Yulia Trunova,

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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  • 3 Vasily Derjabin,

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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  • and 3 Georgy Bakalkin 1

    1. 1 Department of Clinical Neuroscience, Section of Alcohol and Drug Addiction Research, Karolinska Institute, S-171 76, Stockholm, Sweden 2Department of Anatomy and Neurobiology, University of Kentucky, College of Medicine, MN224 Medical Center, Lexington, KY40536–0084, USA 3National Cardiology Research Center, Moscow, 121552, Russia
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: Georgy Bakalkin, as above.
E-mail: Georgy.Bakalkin@cmm.ki.se

Abstract

Opioid effects on cell division in the embryonic cerebral cortex were examined using two experimental approaches: (i) the presence of opioid receptors in the embryonic day 16 mouse neocortex was tested using immunohistochemical techniques; (ii) the values of the indices of [3H]thymidine pulse labelled cells and mitotic indices were estimated in the ventricular zone of the embryonic day 16 mouse neocortex 2.5, 4.5 and 8.5 h after administration to pregnant females of selected opioid receptor agonists or the opioid antagonist naloxone. The immunohistochemical study demonstrated that distinct subpopulations of the ventricular zone cells express μ, δ or κ opioid receptors. Acute exposure of mouse embryos to μ, δ and κ opioid receptor agonists or naloxone differentially affects the indices of [3H] thymidine pulse labelled cells and mitotic indices indicating changes in the cell cycle composition. Treatment with the μ opioid receptor agonist D-Ala2-MePhe4, Gly-ol5-enkephalin (DAGO), or the partially selective κ opioid receptor agonist bremazocine, increased the [3H]thymidine labelling and mitotic indices. In contrast, the δ receptor agonist (D-Ser8)-leucine enkephalin-Thr (DSLET) produced a decrease in the labelled cell indices and mitotic indices. Naloxone provided a biphasic effect: a decrease in the values of labelled cell indices 2.5 h after naloxone administration, followed by an increase in the values of the indices at 4.5 and 8.5 h. These results suggest that the endogenous embryonic/maternal opioid systems are involved in the regulation of cell division in the ventricular zone of the late embryonic cortex.

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