A novel 5-HT receptor or a combination of 5-HT receptor subtypes may mediate depression of a spinal monosynaptic reflex in vitro

Abstract

The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists. The results, together with our previous findings, indicate an apparent rank order of potency: 5-carboxamidotryptamine (5-CT) > sumatriptan > methysergide > 5-HT >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) > 5-methoxytryptamine (5-MeOT) = 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) > alpha-methyl-5-hydroxytryptamine (alpha-Me 5-HT) >> (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The equipotent molar ratios were 5-CT 0.12, sumatriptan 0.4, methysergide 0.72, 5-HT 1.0, 8-OH-DPAT 13.3, 5-MeOT 26.7, TFMPP 31, alpha-Me 5-HT 402 and DOI > 3333. Time for peak depression from start of agonist application was 3-4 min for 5-HT, 5 min for sumatriptan and 5-MeOT, 5-7 min for alpha-Me 5-HT and 12 min for 8-OH-DPAT. The half-time for recovery from peak depression was 1.5 +/- 0.3 min for 5-HT, 2.8 +/- 0.3 min for 5-MeOT, 5.3 +/- 1.5 min for sumatriptan, 13 +/- 2.9 min for 8-OH-DPAT and > 30 min for alpha-Me 5-HT. 8-OH-DPAT induced depression of the reflex (IC50 0.85, 0.7-1.0 microM, geometric mean and 95% confidence limits) was blocked by spiperone (1 microM, apparent pA2 6.3) suggesting mediation via 5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)