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Effects of Morphine on the Differentiation and Survival of Developing Pyramidal Neurons During the Brain Growth Spurt

Massa, Horace ; Lacoh, Claudia-Marvine ; Vutskits, Laszlo

In: Toxicological Sciences, 2012, vol. 130, no. 1, p. 168-179

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    Titel
    • Effects of Morphine on the Differentiation and Survival of Developing Pyramidal Neurons During the Brain Growth Spurt
    Autor
    • Massa, Horace. *Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, 1211 Geneva, Switzerland
    • Lacoh, Claudia-Marvine. †Department of Fundamental Neurosciences, University of Geneva Medical School, 1204 Geneva, Switzerland; and
    • Vutskits, Laszlo. *Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, 1211 Geneva, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Toxicological Sciences, 2012, vol. 130, no. 1, p. 168-179. Oxford University Press
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:295958
    Summary
    Although morphine is frequently administered to treat procedural pain in neonates and young children, little is known about the effects of this drug on developing neural circuitry during the brain growth spurt. Here we systematically explored the impact of morphine on neuronal survival and differentiation during the peak synaptogenic period. By focusing on the rat medial prefrontal cortex, we show that single bolus ip injections of morphine, although it induces deep sedation and analgesia, do not entrain apoptosis in this cortical region either at postnatal day 7 or at postnatal day 15. Iontophoretic single cell injections of Lucifer Yellow followed by semiautomatic neuronal arbor tracing revealed that repeated daily administration of this drug between postnatal days 7 and 15 or 15 and 20 did not interfere with dendritic development of layer 5 pyramidal neurons. Confocal microscopic analysis of dendritic spines at the aforementioned distinct stages of the brain growth spurt demonstrated that neither single bolus nor repeated administration of morphine affected the density of these postsynaptic structures. Altogether, these preclinical rodent experimental observations argue against overt neurotoxic effects of morphine exposure during the brain growth spurt