Increased brain P-glycoprotein in morphine tolerant rats

The objective of this study was to determine whether chronic morphine expos ure increased P-glycoprotein in rat brain. Male Sprague-Dawley rats were tr eated with morphine, saline, or dexamethasone for 5 days. On day 6, antinoc iceptive 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 control s. Brain P-glycoprotein was approximately 2-fold higher in morphine-treated rats compared to saline controls based on Western blot analysis. Chronic m orphine exposure appears to increase P-glycoprotein in rat brain. P-glycopr otein induction may enhance morphine efflux from the brain, thus reducing m orphine's pharmacologic activity. Induction of P-glycoprotein may be one me chanism involved in the development of morphine tolerance. (C) 1999 Elsevie r Science Inc.