Increased brain P-glycoprotein in morphine tolerant rats.
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.
Aquilante
C L
CL
Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.
Letrent
S P
SP
Pollack
G M
GM
Brouwer
K L
KL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009020:Morphine; D003907:Dexamethasone