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

• Published in: British journal of pharmacology 1988-08, Vol.94 (4), p.1101-1114
• Main Authors: Connell, L.A., Wallis, D.I.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn - physiology; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Citalopram - pharmacology; Electrodes; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Ketanserin - pharmacology; Male; Methysergide - pharmacology; Neuromuscular Depolarizing Agents - pharmacology; Norepinephrine - pharmacology; Pargyline - pharmacology; Rats; Serotonin - pharmacology; Serotonin Antagonists - pharmacology; Spinal Cord - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb11628.x

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 mammal