Skip to main content
Log in

Metergoline elevates or reduces nociceptive thresholds in mice depending on test method and route of administration

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Intrathecal injection of metergoline reduced the response latencies in the tail-flick and hot-plate tests, supporting the contention that descending 5-hydroxytryptamine (5-HT) pathways tonically inhibit pain sensitivity. Elevated latencies were, however, observed after both intraperitoneal (IP) and intracerebroventricular (ICV) injections in the hot-plate test, when hindpaw lick was used as the response criterion. These findings may indicate that supraspinal 5-HT pathways tonically increase pain responsiveness in certain test situations. Alternative hypotheses are that metergoline in supraspinal structures acts as an agonist at post-synaptic 5-HT receptors mediating antinociception, or as an antagonist at pre-synaptic 5-HT receptors. Recording of first reaction latencies on the hot-plate showed increased thresholds after IP, but not after ICV injections. This may indicate an action on 5-HT receptors in the brain not accessible after ICV injections, or that the effect is mediated by blockade of peripheral 5-HT receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43

    Google Scholar 

  • Beretta C, Glasser AH, Nobili MB, Silvestri R (1965) Antagonism of 5-hydroxytryptamine-induced bronchospasm in guinea-pigs by 8β-carbobenzyloxyaminomethyl-1,6-dimethyl-10α-ergoline. J Pharm Pharmacol 17:423–428

    Google Scholar 

  • Berge O-G (1982) Effects of 5-HT receptor agonists and antagonists on a reflex response to radiant heat in normal and spinally transected rats. Pain 13:253–266

    Google Scholar 

  • Berge O-G, Fasmer OB, Flatmark T, Hole K (1983a) Time course of changes in nociception after 5,6-dihydroxytryptamine lesions of descending 5-HT pathways. Pharmacol Biochem Behav 18:636–643

    Google Scholar 

  • Berge O-G, Fasmer OB, Hole K (1983b) Serotonin receptor antagonists induce hyperalgesia without preventing morphine antinociception. Pharmacol Biochem Behav 19:873–878

    Google Scholar 

  • Bourgoin S, Artaud F, Bockaert J, Hery F, Glowinski J, Hamon M (1978) Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker. Naunyn-Schmiedeberg's Arch Pharmacol 302:313–321

    Google Scholar 

  • Colpaert FC, Niemegeers CJE, Janssen PAJ (1979) In vivo evidence of partial agonist activity exerted by purported 5-hydroxytryptamine antagonists. Eur J Pharmacol 58:505–509

    Google Scholar 

  • D'Amour FE, Smith DL (1941) A method for determining loss of pain sensation. J Pharmacol Exp Ther 72:74–79

    Google Scholar 

  • Eddy NB, Leimbach D (1953) Synthetic analgesics. II. Dithienyl-butenyl-and dithienylbutylamines. J Pharmacol Exp Ther 107:385–393

    Google Scholar 

  • Ennis C, Cox B (1982) Pharmacological evidence for the existence of two distinct serotonin receptors in rat brain. Neuropharmacology 21:41–44

    Google Scholar 

  • Ennis C, Kemp JD, Cox B (1981) Characterisation of inhibitory 5-hydroxytryptamine receptors that modulate dopamine release in the striatum. J Neurochem 36:1515–1520

    Google Scholar 

  • Fuxe K, Agnati L, Everitt B (1975) Effects of methergoline on central monoamine neurones. Evidence for a selective blockade of central 5-HT receptors. Neurosci Lett 1:283–290

    Google Scholar 

  • Griersmith BT, Duggan AW, North RA (1981) Methysergide and supraspinal inhibition of the spinal transmission of nociceptive information in the anaesthetized cat. Brain Res 204:147–158

    Google Scholar 

  • Göthert M (1980) Serotonin-receptor-mediated modulation of Ca2+-dependent 5-hydroxytryptamine release from neurones of of the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 314:223–230

    Google Scholar 

  • Haigler HJ, Aghajanian GK (1974) Peripheral serotonin antagonists: Failure to antagonize serotonin in brain areas receiving a prominent serotonergic input. J Neural Transm 35:257–273

    Google Scholar 

  • Haley TJ, McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol 12:12–15

    Google Scholar 

  • Herman ZS (1975) Behavioural changes induced in conscious mice by intracerebroventricular injection of catecholamines, acetylcholine and 5-hydroxytryptamine. Br J Pharmacol 55:351–358

    Google Scholar 

  • Hole K, Lorens SA (1975) Response to electric shock in rats: Effects of selective midbrain raphe lesions. Pharmacol Biochem Behav 3:95–102

    Google Scholar 

  • Hole K, Fuxe K, Jonsson G (1976) Behavioural effects of 5,7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways. Brain Res 107:385–399

    Google Scholar 

  • Hylden JLK, Wilcox GL (1980) Intrathecal morphine in mice: A new technique. Eur J Pharmacol 67:313–316

    Google Scholar 

  • Lin M-T, Chandra A, Chi M-L, Kau C-L (1980) Effects of increasing serotonergic receptor activity in brain on analgesic activity in rats. Exp Neurol 68:548–554

    Google Scholar 

  • Malec D, Langwinski R (1980) The influence of 5-HT receptor blocking agents on the behavioural effects of analgesics in rats. Psychopharmacology 69:79–83

    Google Scholar 

  • Messing RB, Lytle LD (1977) Serotonin-containing neurons: Their possible role in pain and analgesia. Pain 4:1–21

    Google Scholar 

  • Mounsey I, Brady KA, Carroll J, Fisher R, Middlemiss DN (1982) K+-evoked [3H]-5-HT release from rat frontal cortex slices: The effect of 5-HT agonists and antagonists. Biochem Pharmacol 31:49–53

    Google Scholar 

  • Nakano T, Taira N (1976) 5-Hydroxytryptamine as a sensitizer of somatic nociceptors for pain-producing substances. Eur J Pharmacol 38:23–29

    Google Scholar 

  • Proudfit HK (1980) Reversible inactivation of raphe magnus neurons: effects on nociceptive threshold and morphine-induced analgesia. Brain Res 201:459–464

    Google Scholar 

  • Proudfit HK, Hammond DL (1981) Alterations in nociceptive threshold and morphine-induced analgesia produced by intrathecally administered amine antagonists. Brain Res 218:393–399

    Google Scholar 

  • Rochat C, Cervo L, Romandini S, Samanin R (1982) Differences in the effects of d-fenfluramine and morphine on various responses of rats to painful stimuli. Psychopharmacology 76:188–192

    Google Scholar 

  • Samanin R, Bernasconi S, Quattrone A (1976) Antinociceptive action of quipazine: Relation to central serotonergic receptor stimulation. Psychopharmacologia 46:219–222

    Google Scholar 

  • Sastry BSR, Phillis JW (1977) Metergoline as a selective 5-hydroxytryptamine antagonist in the cerebral cortex. Can J Physiol Pharmacol 55:130–133

    Google Scholar 

  • Simansky KJ, Harvey JA (1981) Altered sensitivity to footshock after selective serotonin depletion: Comparison of electrolytic lesions and neurotoxin injections in the medial forebrain bundle of the rat. J Comp Physiol Psychol 95:341–350

    Google Scholar 

  • Soja PJ, Sinclair JG (1980) Evidence against a serotonin involvement in the tonic descending inhibition of nociceptor-driven neurons in the cat spinal cord. Brain Res 199:225–230

    Google Scholar 

  • Spano PF, Biggio G, Casu M, Gessa GL, Bareggi SR, Govoni S, Trabucchi M (1978) Interaction of metergoline with striatal dopamine system. Life Sci 23:2383–2392

    Google Scholar 

  • Yaksh TL, Wilson PR (1979) Spinal serotonin terminal system mediates antinociception. J Pharmacol Exp Ther 208:446–453

    Google Scholar 

  • York JL, Maynert EW (1978) Alterations in morphine analgesia produced by chronic deficits of brain catecholamines or serotonin: Role of analgesimetric procedure. Psycho-pharmacology 56:119–125

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fasmer, O.B., Berge, O.G. & Hole, K. Metergoline elevates or reduces nociceptive thresholds in mice depending on test method and route of administration. Psychopharmacology 82, 306–309 (1984). https://doi.org/10.1007/BF00427675

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00427675

Key words

Navigation