Pharmacogenetic evidence for the involvement of 5-hydroxytryptamine (serotonin)-1B receptors in the mediation of morphine antinociceptive sensitivity

Heather S. Hain, John Belknap, Jeffrey S. Mogil

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Abstract

Morphine antinociception has been shown to be influenced significantly by genetic factors, now beginning to be identified in mice. A recent quantitative trait locus analysis revealed a significant statistical association between morphine antinociceptive magnitude and a region of mouse chromosome 9. This region contains the Htr1b gene, which encodes the 5- hydroxytryptamine (serotonin)-1B (5-HT(1B)) receptor subtype. To investigate the possibility that Htr1b represents the quantitative trait locus, C57BL/6 and DBA/2 inbred strains, the progenitors of the original quantitative trait locus mapping populations, were administered a novel 5-HT(1B) receptor antagonist (GR127935) concomitant with morphine. These mice are known to differ in morphine antinociceptive sensitivity on thermal pain assays (DBA/2 high; C57BL/6 low). GR127935 caused a dose-dependent antagonism (both reversal and prevention) of morphine antinociception in DBA/2 mice but had no effect in C57BL/6 mice. However, a 5-hydroxytryptamine-1A subtype (5-HT(1A)) receptor agonist, 8-hydroxydipropylaminotetralin, reversed morphine antinociception equally in the two strains. DBA/2 mice also exhibited significantly greater antinociception than did C57BL/6 mice from the administration of a 5-HT(1B) agonist, CGS12066. These data collectively support a role for 5-HT(1B) receptors in the mediation of morphine antinociception and support the contention that polymorphisms in the Htr1b gene may underlie individual differences in morphine sensitivity.

Original languageEnglish (US)
Pages (from-to)444-449
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume291
Issue number2
StatePublished - Nov 1999

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Receptor, Serotonin, 5-HT1B
Pharmacogenetics
Morphine
Quantitative Trait Loci
Inbred DBA Mouse
Inbred C57BL Mouse
Serotonin
Serotonin Receptor Agonists
Chromosomes, Human, Pair 9
Receptor, Serotonin, 5-HT1A
Individuality
Genes
Hot Temperature
Pain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pharmacogenetic evidence for the involvement of 5-hydroxytryptamine (serotonin)-1B receptors in the mediation of morphine antinociceptive sensitivity. / Hain, Heather S.; Belknap, John; Mogil, Jeffrey S.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 291, No. 2, 11.1999, p. 444-449.

Research output: Contribution to journalArticle

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