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  • Title: Kappa opioid analgesia is dependent on serotonergic mechanisms.
    Author: Vonvoigtlander PF, Lewis RA, Neff GL.
    Journal: J Pharmacol Exp Ther; 1984 Nov; 231(2):270-4. PubMed ID: 6092612.
    Abstract:
    The serotonergic dependence of mu and kappa opioid analgesia was compared in the mouse tail-flick and hot-plate assays using morphine and the selective kappa agonist, U-50, 488H, respectively. Depletion of serotonin with p-chlorophenylalanine resulted in a marked antagonism of U-50,488H analgesic potency in both assays, as did reserpine pretreatment. Both of these effects were dose-related and the latter was reversed by treatment with the serotonin precursor, 5-hydroxytryptophan. Several reputed serotonin antagonists (cyproheptadine, ketanserin and pirenperone) also antagonized U-50,488H analgesia. In contrast, the analgesic potency of morphine was only decreased slightly by p-chlorophenylalanine and reserpine, and not at all by the serotonin antagonists. Thus, kappa, but not mu, analgesia is strongly dependent upon serotonergic mechanisms in these assays. However 5-hydroxytryptophan did not enhance U-50,488H analgesia in nonpretreated mice or in mice made tolerant to U-50,488H. Likewise, it did not alter the development of U-50,488H tolerance. On this basis it appears that kappa opioid tolerance is not due to serotonergic hypofunction.
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