RT Journal Article
SR Electronic
T1 Tolerance to intrathecal oxymetazoline-induced analgesia, with paradigm-dependent cross-tolerance to intrathecal morphine.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 319
OP 326
VO 245
IS 1
A1 S E Sherman
A1 C W Loomis
A1 B Milne
A1 F W Cervenko
YR 1988
UL http://jpet.aspetjournals.org/content/245/1/319.abstract
AB Male, Sprague-Dawley rats, implanted with intrathecal (i.t.) catheters, were given repeated i.t. injections of morphine (40 nmol), oxymetazoline (100 nmol) or saline (10 microliter) at 12-h intervals for 3 days. Antinociception was determined 1 or 1.5 hr after each injection using the tail-flick and paw-pressure tests. Complete tolerance to i.t. morphine and oxymetazoline developed within 72 and 24 hr, respectively. Antinociception after i.t. oxymetazoline (100 nmol) in morphine-tolerant rats, and after i.t. morphine (20 nmol) in oxymetazoline-tolerant rats, was not significantly different from their respective effects in saline-pretreated rats. These data suggest an absence of cross-tolerance between morphine and oxymetazoline in the rat spinal cord. In a separate group of rats, the continuous i.t. infusion of morphine (26 nmol/hr) produced significant antinociception; tolerance to morphine developed within 36 hr. The antinociceptive effect of i.t. oxymetazoline (100 nmol) was significantly attenuated in rats pretreated with continuous i.t. morphine as compared to saline-pretreated rats. In rats pretreated with continuous i.t. oxymetazoline, cross-tolerance to morphine could not be determined due to severe adverse effects during oxymetazoline infusion. The results of this study suggest that functional cross-tolerance between morphine and alpha adrenoceptor agonists in the spinal cord cannot be excluded on the basis of repeated i.t. injection experiments alone.