Skip to main content
Log in

Selective effects of pirenperone on analgesia produced by morphine or electrical stimulation at sites in the nucleus raphe magnus and periaqueductal gray

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

Abstract

Pirenperone, a new serotonin antagonist with a selective affinity for the 5-HT2 receptor, was administered in conjunction with tests for the antinociceptive effects of morphine sulphate and electrical brain-stimulation at sites in the periaqueductal gray (PAG) and nucleus raphe magnus (NRM). Nociception was assessed by tail-flick latencies in a warm water bath and pirenperone (0.04–0.16 mg/kg) had no effect on baseline scores. When administered prior to morphine, pirenperone (0.16 mg/kg) caused significant attenuation of analgesia induced by morphine. Comparable effects of pirenperone were observed when analgesia was produced by electrical stimulation of the NRM. In contrast, pirenperone had no effect on the analgesic effects of PAG stimulation. This pattern of results suggests that a system involving supraspinal 5-HT2 receptors may modulate some of the antinociceptive effects of morphine and stimulation of the NRM. The differential effects of pirenperone on stimulation-produced analgesia at sites in the NRM and PAG is consistent with separate neural substrates for the analgesia observed from stimulation of these two brain regions.

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

  • Basbaum AI, Fields HL (1984) Endogenous pain control systems: Brainstem spinal pathways and endorphin circuitry. Ann Rev Neurosci 7:309–338

    Google Scholar 

  • Berge OG, Fasmer OB, Kjell H (1983) Serotonin receptor antagonists induce hyperalgesia without preventing morphine antinociception. Pharmacol Biochem Behav 19:873–878

    Google Scholar 

  • Colpaert FC, Janssen PAJ (1983) The head-twitch response to intraperitoneal injection of 5-hydroxytryptophan in the rat: Antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist. Neuropharmacology 22:993–1000

    Google Scholar 

  • Colpaert FC, Niemgeers CJE, Janssen PAF (1982) A drug discrimination analysis of lysergic acid diethylamide (LSD): In vivo agonist and antagonist effects or purported 5-hydroxytryptamine antagonists and of pirenperone, a LSD-antagonist. J Pharmacol Exp Ther 221:206–214

    Google Scholar 

  • Dickenson AA, Oliveras JL, Besson JM (1979) Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat. Brain Res 170:95–111

    Google Scholar 

  • Gorlitz BD, Frey HH (1972) Central monoamines and antonociceptive drug action. Eur J Pharmacol 20:171–180

    Google Scholar 

  • Green AR, O'Shaughnessy K, Hammond M, Schachter M, Grahame-Smith DG (1983) Inhibition of 5-hydroxytryptamine-mediated behavior by the putative 5-HT2 antagonist pirenperone. Neuropharmacology 22:573–578

    Google Scholar 

  • Hammond DL, Yaksh TL (1984) Antagonism of stimulation-produced antinociception by intrathecal administration of methysergide or phentolamine. Brain Res 298:329–337

    Google Scholar 

  • Janssen PAJ (1983) 5-HT2 receptor blockade to study serotonin-induced pathology. TIPS 4:198–206

    Google Scholar 

  • Leysen JE, Awouters F, Kennis L, Laduron PM, Vandenberk J, Janssen PAJ (1981) Receptor binding profile of R41468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Tollenaeize JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature (Lond.) 272:168–171

    Google Scholar 

  • Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) [3H] ketanserin (R41468), a selective3H-ligand for serotonin2 receptor binding sites. Mol Pharmacol 21:301–314

    Google Scholar 

  • Mayer DJ, Wolfle TL, Akil H, Carder G, Liebeskind JC (1971) Analgesia from electrical stimulation in the brainstem of the rat. Science 174:1351–1354

    Google Scholar 

  • Monroe PJ, Smith DJ (1983) Characterization of multiple [3H] 5-hydroxytryptamine binding sites in rat spinal cord tissue. J Neurochem 41:349–355

    Google Scholar 

  • Oliveras JL, Bourgoin S, Hery F, Besson JM, Hamon M (1979) A map of serotonergic structures involved in stimulation producing analgesia in unrestrained freely moving cats. Brain Res 164:317–322

    Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic co-ordinates. Academic Press, New York

    Google Scholar 

  • Pellegrino LJ, Cushman AJ (1967) A stereotaxic atlas of the rat brain. Appleton-Century-Crofts, New York

    Google Scholar 

  • Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829

    Google Scholar 

  • Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: Differential binding of [3H] 5-hydroxytryptamine, [3H] lysergic acid diethylamide and [3H] spiroperidol. Mol Pharmacol 16:687–699

    Google Scholar 

  • Plotkin KE, Thorn-Gray BE (1983) The neurochemical mechanism for stimulation-produced analagesia: Comparison of tests involving tonic and phasic pain. Neurosci Abst 9:261.2

    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 

  • Reynolds DV (1969) Surgery in the rat during analgesia induced by focal brain stimulation. Science 164:444–445

    Google Scholar 

  • Satoh M, Akaike A, Nakazawa T, Takagi H (1980) Evidence for involvement of separate mechanism in the production of analgesia by electrical stimulation of the nucleus reticularis paragigantocellularis and nucleus raphe magnus in the rat. Brain Res 194:525–529

    Google Scholar 

  • Shiomi H, Takagi H (1974) Morphine analgesia and bulbospinal noradrenergic system: Increase in the concentration of normetanephrine in the spinal cord of the rat caused by analgesia. Br J Pharmacol 52:519

    Google Scholar 

  • Yaksh TL (1979) Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinocieceptive effects of morphine in the periaqueductal gray. Brain Res 160:180–185

    Google Scholar 

  • Yaksh TL, DuChateau JC, Rudy TA (1976) Antagonism by methysergide and cinanserin of the antinociceptive action of morphine administered into the periaqueductal gray. Brain Res 104:367–372

    Google Scholar 

  • Yeung JC, Yaksh TL, Rudy T (1977) Concurrent mapping of brain stem sites for sensitivity to the direct application of morphine and focal electrical stimulation in the production of antonociception in the rat. Pain 4:23–40

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paul, D., Phillips, A.G. Selective effects of pirenperone on analgesia produced by morphine or electrical stimulation at sites in the nucleus raphe magnus and periaqueductal gray. Psychopharmacologia 88, 172–176 (1986). https://doi.org/10.1007/BF00652235

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00652235

Key words

Navigation