TY - JOUR T1 - Pharmacogenetic Evidence for the Involvement of 5-Hydroxytryptamine (Serotonin)-1B Receptors in the Mediation of Morphine Antinociceptive Sensitivity JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 444 LP - 449 VL - 291 IS - 2 AU - Heather S. Hain AU - John K. Belknap AU - Jeffrey S. Mogil Y1 - 1999/11/01 UR - http://jpet.aspetjournals.org/content/291/2/444.abstract N2 - 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 theHtr1b gene, which encodes the 5-hydroxytryptamine (serotonin)-1B (5-HT1B) 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-HT1B 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-HT1A) 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-HT1B agonist, CGS12066. These data collectively support a role for 5-HT1Breceptors in the mediation of morphine antinociception and support the contention that polymorphisms in the Htr1b gene may underlie individual differences in morphine sensitivity. The American Society for Pharmacology and Experimental Therapeutics ER -