Increased brain P-glycoprotein in morphine tolerant rats

Life Sci. 2000;66(4):PL47-51. doi: 10.1016/s0024-3205(99)00599-8.


The objective of this study was to determine whether chronic morphine exposure increased P-glycoprotein in rat brain. Male Sprague-Dawley rats were treated with morphine, saline, or dexamethasone for 5 days. On day 6, antinociceptive effect was measured to evaluate the extent of functional tolerance to morphine. Brain P-glycoprotein was detected by Western blot analysis of whole brain homogenate. Morphine- and dexamethasone-treated rats exhibited decreased antinociceptive response when compared to saline-treated controls. Brain P-glycoprotein was approximately 2-fold higher in morphine-treated rats compared to saline controls based on Western blot analysis. Chronic morphine exposure appears to increase P-glycoprotein in rat brain. P-glycoprotein induction may enhance morphine efflux from the brain, thus reducing morphine's pharmacologic activity. Induction of P-glycoprotein may be one mechanism involved in the development of morphine tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis*
  • Animals
  • Brain Chemistry / drug effects*
  • Dexamethasone / pharmacology
  • Drug Tolerance
  • Male
  • Morphine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Morphine
  • Dexamethasone