Intrathecal 5-methoxy-N, N-dimethyltryptamine in mice modulates 5-HT1 and 5-HT3 receptors

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Abstract

The antinociceptive effects of intrathecally administered 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), a potent 5-HT receptor agonist, were studied in three behavioral tests in mice: the tail-flick test and the intrathecal substance P and N-methyl-D-aspartic acid (NMDA) assays. Intrathecal administration of 5-MeO-DMT (4.6–92 nmol/mouse) produced a significant prolongation of the tail-flick latency. This action was blocked by 5-HT3 and γ-aminobutyric acidA (GABAA) receptor antagonists but not by 5-HT2, 5-HT1A, 5-HT1B or 5-HT1S receptor antagonists. Binding studies indicated that 5-MeO-DMT had very low affinity for 5-HT3 receptors. 5-MeO-DMT inhibited biting behavior while increasing scratching behavior induced by intrathecally administered substance P. The inhibition of biting behavior was antagonized by intrathecal co-administration of 5-HT1B and GABAA receptor ntagonists while 5-HT1A, 5-HT1S, 5-HT2 and 5-HT3 receptor antagonists had no effect. 5-MeO-DMT-enhanced scratching behavior was inhibited by all the antagonists used except ketanserin and bicuculline, suggesting the involvement of 5-HT1A, 5-HT1B, 5-HT1S, 5-HT3 and GABAA receptors. NMDA-induced biting behavior was inhibited by 5-MeO-DMT pretreatment; this action was antagonized by 5-HT1B, 5-HT3 and GABAA receptor antagonists. The involvement of these receptors in 5-MeO-DMT action suggests that it may promote release of 5-HT (5-hydroxytryptamine, serotonin).

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    Part of this work was presented at the 72nd Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics, Milwaukee, WI, USA, August, 1990.

    1

    Present address: Department of Medical Pharmacology, School of Medicine, King Saud University, P.O. Box 2925, Riyadh, Saudi Arabia.

    2

    Present address: Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpetrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.

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