Effect of chronic administration of morphine on the gene expression level of sodium-dependent vitamin C transporters in rat hippocampus and lumbar spinal cord

J Mol Neurosci. 2009 Jul;38(3):236-42. doi: 10.1007/s12031-009-9203-x. Epub 2009 May 6.

Abstract

Chronic morphine leads to dependence, tolerance, and neural apoptosis. Vitamin C inhibits the withdrawal syndrome in morphine-dependent subjects and prevents apoptosis in experimental models. Sodium-dependent vitamin C transporter (SVCT) type-2 is the main transporter for carrying vitamin C into the brain and neural cells. The mechanism(s) by which vitamin C inhibits morphine dependence in not understood. SVCT activity determines the vitamin C availably within the nervous system. We have examined the alterations in the expression of SVCT1, SVCT2, and its splice variants in morphine-tolerant rats. Morphine (20 mg/kg) was injected twice/day to male rats for either 7 or 14 days. The development of analgesic tolerance was assessed using tail-flick test. Lumbar spinal cord and the hippocampus were isolated for RNA extraction. Semiquantitative reverse transcriptase-polymerase chain reaction method was used to assess the levels of gene expression. Administration of morphine for 7 or 14 days reduced the expression level of SVCT2 in both hippocampus and dorsal lumbar spinal cord of rats. SVCT2 expression was reduced in vitamin C-, and vitamin C combined with morphine-treated animals. Results did not show SVCT2 splice variation. SVCT1 did not express in control or morphine-treated rats. It seems that reduced expression level of SVCT2 might be involved in the development of morphine side effects such as tolerance and dependency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Drug Tolerance / physiology
  • Gene Expression / drug effects*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Humans
  • Lumbar Vertebrae
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Pain Measurement
  • Rats
  • Rats, Wistar
  • Sodium-Coupled Vitamin C Transporters
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Symporters / genetics*
  • Symporters / metabolism

Substances

  • Analgesics, Opioid
  • Organic Anion Transporters, Sodium-Dependent
  • SLC23A1 protein, human
  • SLC23A2 protein, human
  • Slc23a1 protein, rat
  • Slc23a2 protein, rat
  • Sodium-Coupled Vitamin C Transporters
  • Symporters
  • Morphine