Peripheral 5-carboxamidotryptamine induces hindlimb scratching by stimulating 5-HT 1A receptors in rats

Abstract

Treatment of rats with 5-carboxamidotryptamine (5-CT) or 5-methoxytryptamine (5-MeOT) induces a hindlimb scratch response. These compounds have high affinity for 5-HT 1A and 5-HT 1D receptors. The selective 5-HT 1A receptor agonist N,N-dipropyl-5-CT (DP-5-CT) also induced hindlimb scratching while the selective 5-HT 1D HD 1D receptor agonist, sumatriptan, did not. 5-CT-induced hindlimb scratching was inhibited dose-dependently by several 5-HT 1A antagonists (BMY 7378, NAN-190, MDL 73005EF and pindobind-5-HT 1A) as well as the non-selective 5-HT antagonist, methiothepin. Pretreatment of rats with the serotonin (5-HT) synthesis inhibitor, p- chlorophenylalanine (PCPA) or the 5-HT depleting agent, reserpine, markedly attenuated 5-CT-induced hindlimb scratching. These data suggest that hindlimb scratching induced by 5-HT agonists may not be centrally mediated but rather may be mediated by a neuronal 5-HT 1A receptor localized outside the blood-brain barrier.