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5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats

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Summary

The antinociceptive effect elicited by the 5-hydroxytryptamine (5-HT) agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was reversed or blocked in animals which had previously sustained severe spinal noradrenaline (NA) depletion via either systemic N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4), neonatal 6-hydroxydopamine (neon. 6-OHDA), or intrathecal 6-OHDA treatment. Biochemical analysis of the lumbar spinal cord samples confirmed severe central NA depletions. Animals were tested with nondamaging heat pain (tail-flick test, hot-plate test) and electric footshock titration to determine the amount of antinociception or nociception. Peripheral NA depletion following intravenous (i.v.) 6-OHDA injection to adult rats had no effect on the antinociception induced by 5-MeODMT, but did cause severe NA depletions in the left heart atrium. These results suggest a modulatory effect of central and not peripheral noradrenergic system upon 5-HT agonist induced analgesia, and also give evidence that this effect is spinally mediated.

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Author notes

  1. B. G. Minor

    Present address: Department of Pharmacology, AB Astra Läikemedel, S-151 85, Södertälie, Sweden

Authors and Affiliations

  1. R and D Laboratories, Astra Alab AB, Södertälje, Sweden

    B. G. Minor, T. Archer, C. Post, G. Jonsson & A. K. Mohammed

  2. Department of Histology, Karolinska Institutet, Stockholm, Sweden

    G. Jonsson

  3. Neurophysiological Laboratory, Ulleråkers Sjukhus, Uppsala, Sweden

    A. K. Mohammed

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  1. B. G. Minor
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  2. T. Archer
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  3. C. Post
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  4. G. Jonsson
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  5. A. K. Mohammed
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Minor, B.G., Archer, T., Post, C. et al. 5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats. J. Neural Transmission 66, 243–259 (1986). https://doi.org/10.1007/BF01260917

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  • DOI: https://doi.org/10.1007/BF01260917

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