Abstract:
:The effect of intracerebroventricular administration of low-antinociceptive doses of selective mu- (DAMGO) or delta- (DPDPE) opioid agonists on the dose-dependent antinociceptive effects produced by intrathecal administration of sequentially increasing doses of selective mu-, delta-, or kappa-(U50,488H) opioid agonists was evaluated, in the rat, using the Randall-Selitto paw-withdrawal test. When DPDPE or U50,488H was administered intrathecally, the low doses of both intracerebroventricular DAMGO and intracerebroventricular DPDPE markedly enhanced the antinociceptive effects of both intrathecal opioids. In contrast, when DAMGO was administered intrathecally, both intracerebroventricular DAMGO and intracerebroventricular DPDPE, administered in low doses, markedly antagonized the antinociceptive effects of the intrathecal opioid. In addition, the intracerebroventricular administration of a low-antinociceptive dose of a second mu-opioid agonist, morphiceptin, antagonized the antinociceptive effects of intrathecal morphiceptin. The antagonism of the antinociceptive effects observed with spinal administration of DAMGO is dose-dependent, with the effect observed only at low doses. Furthermore, the antagonism cannot be explained by a reduction in motor deficits produced by intrathecal administration of DAMGO, because there were no differences in motor deficits, measured with an accelerating Rotarod treadmill, between intrathecal DAMGO administered as a single agent or as part of a combination regimen. The differences in antinociceptive effects obtained with the various supraspinal and spinal combinations are discussed in terms of the interactions that may occur between brainstem and spinal opioid receptor sites.
journal_name
Brain Resjournal_title
Brain researchauthors
Miaskowski C,Levine JDdoi
10.1016/0006-8993(92)91449-osubject
Has Abstractpub_date
1992-11-06 00:00:00pages
32-8issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(92)91449-Ojournal_volume
595pub_type
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