RT Journal Article
SR Electronic
T1 Relationship of brain morphine levels to analgesic activity in acutely treated mice and rats and in pellet implanted mice.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 876
OP 883
VO 193
IS 3
A1 G A Patrick
A1 W L Dewey
A1 T C Spaulding
A1 L S Harris
YR 1975
UL http://jpet.aspetjournals.org/content/193/3/876.abstract
AB The relationship of brain morphine concentration, determined fluorometrically, to tail-flick activity was investigated after acute and chronic morphine treatment of mice and acute treatment of rats. Brain morphine levels were quantitatively related to the analgesic effect on acute administration, with levels of 100 and 140 ng/g of tissue corresponding to the ED50 in mice and rats, respectively. Over a 90-minute time course after acute s.c. injection, the analgesic effect of morphine in the tail-flick test lagged slightly behind morphine brain level in both species. In mice implanted s.c. with morphine pellets, significant analgesia and appreciable morphine brain levels appeared as early as 20 to 30 minutes after implantation. Increased brain morphine corresponded to increased analgesia at 1 and 4 hours after implantation. Tolerance was evident by 24 hours after implantation and was maximal at 72 hours. Brain morphine remained elevated up to 144 hours after implantation even though substantial encapsulation of the pellet occurred within 72 hours. If pellets were removed at 72 hours, brain morphine declined to control levels with 6 hours, but significant tolerance persisted for at least 24 hours after pellet removal. These results demonstrate that morphine is absorbed from the pellet up to 6 days after implantation and that the decreased analgesic activity observed in the latter times is due to tolerance to the narcotic and not to a decrease in absorption from the pellet.