Abstract
The pharmacological characteristics of hindlimb scratching induced by serotonergic compounds were studied. We conclude that hindlimb scratching induced by serotonergic compounds is mediated by a serootonin 1D (5-HT 1D) or 5-HT 1D-like receptor outside the blood-brain barrier because hindlimb scratching could be induced by s.c. injection of 5-methoxytryptamine (5-MeOT), 5-carboxamidotryptamine (5-CT), bufotenine, 5-hydroxytryptamine (5-HT) and tryptamine. These compounds have high affinity for 5-HT 1A and 5-HT 1D receptors. The 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT 1C receptor agonist MK 212, and the mixed 5-HT 1C/5-HT 2 receptor agonists (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and quipazine did not induce hindlimb scratching. Rather, the latter compounds attenuated 5-MeOT-induced hindlimb scratching. The 5-HT releasing compounds fenfluramine and p-chloroamphetamine (PCA) inhibited whereas the 5-HT re-uptake inhibitors fluvoxamine and indalpine potentiated 5-MeOT-induced hindlimb scatching, 5-MeOT-induced hindlimb scratching could be inhibited dose dependently by the α- 2-adrenoceptor blockers yohimbine and rauwolsince, which also have high affinity for 5-HT 1D receptors, whereas the α 2-adrenoceptor blocker piperoxan only weakly counteracted hindlimb scratching. Haloperidol, apomorphine, morphine, clonidine and methiothepin strongly attenuated hindlimb scratching, atropine, naloxone and ICS 205930 attenuated it weakly whereas domperidone, methylatropine and mepyramine were inactive in doses up to 10 mg/kg. Hindlimb scratching induced by 5-MeOT was potentiated by the 5-HT receptor antagonists metergoline, methysergide, mesulergine, mianserin, ritanserin and xylamidine. Hindlimb scratching was not induced by i.c.v. injection of 5-MeOT. This lack of i.c.v. activity of 5-MeOT and the effect of xylamidine suggests that the site of action for induction of hindlimb scratching is outside the blood-brain barrier.
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