Neonatal morphine exposure alters E-NTPDase activity and gene expression pattern in spinal cord and cerebral cortex of rats

Eur J Pharmacol. 2010 Sep 10;642(1-3):72-6. doi: 10.1016/j.ejphar.2010.05.044. Epub 2010 Jun 8.

Abstract

The neonate opioid system has been frequently investigated, and studies have shown that exposure to drugs in early life can have implications for nervous system development. It has been proposed that adenosine is involved in opioid antinociception, and ATP is involved in central and peripheral mechanisms of nociception. Extracellular nucleotides can be hydrolyzed by E-NTPDases and ecto-5'nucleotidase, which present the functions of removing ATP and generating adenosine. In this study, we evaluated ATP, ADP, and AMP hydrolysis in synaptosomes from spinal cord and cerebral cortex of rats at postnatal day 16 after repeated morphine exposure in early life (postnatal day 8 to 14). Additionally, we evaluated E-NTPDase (1, 2 and 3) and ecto-5'nucleotidase gene expression by semi-quantitative RT-PCR analysis. We observed an increase in ATP hydrolysis in the cerebral cortex, and a decrease in ADP hydrolysis in spinal cord. Expression levels of E-NTPDase 1 decreased in cerebral cortex and increased in spinal cord. Our findings highlight the importance of the purinergic system in young rats submitted to repeated morphine exposure by showing that in the neonatal period such exposure is capable of affecting the control system for nucleotide levels, which can promote changes in modulation or transmission of painful stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / genetics*
  • Acid Anhydride Hydrolases / metabolism*
  • Animals
  • Animals, Newborn
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Male
  • Morphine / pharmacology*
  • Rats
  • Rats, Wistar
  • Spinal Cord / cytology
  • Spinal Cord / drug effects*
  • Spinal Cord / enzymology
  • Spinal Cord / metabolism
  • Synaptosomes / drug effects
  • Synaptosomes / enzymology
  • Synaptosomes / metabolism
  • Time Factors

Substances

  • Morphine
  • Acid Anhydride Hydrolases