| Autor: |
Sherman, S E, Loomis, C W, Milne, B, Cervenko, F W |
| Zdroj: |
The Journal of Pharmacology and Experimental Therapeutics; April 1988, Vol. 245 Issue: 1 p319-326, 8p |
| Abstrakt: |
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. |
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