Responses to 5‐hydroxytryptamine evoked in the hemisected spinal cord of the neonate rat

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Abstract
1 Superfusion of isolated hemisected spinal cord from neonate rats with 5-hydroxytryptamine (5-HT) (10−6 to 10−3 m) evoked concentration-related depolarizations. The maximal depolarization elicited by a concentration of 10−4 m was 1.0 ± 0.1 mV (mean ± s.e.mean, n = 30). Noradrenaline in a similar range of concentrations also elicited depolarizations. 2 The depolarizations probably originate in motoneurones as a result of direct interaction of the amines with these cells, since responses were unaltered by tetrodotoxin (10−7 m) or Ca2+-free/Mg2+-rich medium. 3 5-Carboxamidotryptamine (5-CT), S(+)−α-methyl-5-hydroxytryptamine (α-Me5-HT) and 5-methoxytryptamine (5-MeOT) evoked similar depolarizations to 5-HT. Tryptamine evoked depolarizations of smaller maximal amplitude. 5-Hydroxytryptophan, 2-methyl-5-hydroxytryptamine, 8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide (8-OH-DPAT) and 5-methoxy-3-[1,2,3,6-tetrahydro-4-pyridinyl]-1-H-indole succinate (RU 24969) had no depolarizing action. 4 Concentration-response (CR) curves were determined for 5-HT, 5-CT, α-Me5-HT, 5-MeOT and tryptamine. The ED50 value for 5-HT was 20.5 ± 1.2 μm. The equipotent molar ratios (EPMRs) for 5-CT and α-Me5-HT were close to unity, while 5-MeOT was approximately 3 times and tryptamine 13 to 14 times less potent than 5-HT. 5 The relative agonist potency of 5-HT with respect to other tryptamine analogues capable of depolarizing motoneurones was increased when 5-HT uptake was blocked by citalopram (10−7 m). In the presence of citalopram, 5-HT was 2.7 times more potent than α-Me5-HT and 16.9 times more potent than 5-CT. The apparent order of potency was 5-HT > α-Me5-HT > 5-CT (> 5-MeOT > tryptamine). 6 The monoamine oxidase inhibitor, pargyline (5 × 10−4 m), had no effect on depolarizations to 5-HT, 5-CT or α-Me5-HT. 7 Methiothepin, 1αH, 3α, 5H-tropan-3-yl-3,5-dichlorobenzoate methanesulphonate (MDL 72222) and [3α-tropanyl]-1H-indole-3-carboxylic acid ester hydrochloride (ICS 205–930) had no effect on 5-HT depolarizations elicited in motoneurones. Ketanserin (0.75 × 10−7 m to 10−6 m) showed modest antagonistic action and depressed maximal response amplitude; the pIC50 was 6.5. 8 Methysergide (10−8 to 10−7 m) was a potent antagonist of responses to 5-HT. CR curves were displaced to the right and flattened in the presence of the antagonist. The pIC50 assessed from the effect on depolarizations evoked by 5-HT 10−4 m was 7.5. 9 It is concluded that 5-HT acts directly to depolarize mammalian spinal motoneurones through receptors that are also activated by 5-CT, α-Me5-HT and 5-MeOT and are blocked by methysergide. The receptor profile, although not 5-HT3-like, does not clearly coincide with that for either 5-HT1-like or 5-HT2 receptors.