Further studies on the action of 5-hydroxytryptamine on lumbar motoneurones in the rat isolated spinal cord.

Using the hemisected spinal cord of the neonate rat, the effects of altered external Ca, thyrotrophin-releasing hormone (TRH) and a number of antagonists were tested on depolarizations evoked by 5-hydroxytryptamine (5-HT). Responses of populations of motoneurones were recorded via a ventral root. 5-Hydroxytryptamine depolarizations were not Ca-dependent but were enhanced in amplitude in Ca-free solutions. Raised Mg reversed this enhancement. 5-Hydroxytryptamine depolarizations persisted in the presence of Mn (1.5-3 mmol/l). TRH depolarized motoneurones; there was no evidence of modulation of 5-HT responses on concurrent application of TRH. Ritanserin (0.1 mumol/l) had a modest blocking action on 5-hydroxytryptamine depolarizations reducing the maximum; 1 mumol/l ritanserin caused a greater antagonism which was unsurmountable (pIC50 5.2). Ritanserin (0.1 or 1 mumol/l) did not depress responses to noradrenaline (NA). Ketanserin (0.1 mumol/l) caused a blockade of slow onset, equilibrium with the receptors requiring 1 h. Blockade by 0.01, 0.1 and 1 mumol/l ketanserin was concentration-dependent (pIC50 6.2). Ketanserin 1 mumol/l, but not at lower concentrations, depressed noradrenaline responses. Mianserin (0.1 mumol/l) also caused a blockade of slow onset; 0.1 or 1 mumol/l produced a flattening of the 5-hydroxytryptamine concentration-response curve but did not depress noradrenaline responses (pIC50 4.7). The pIC50 for spiperone was 8.0. DOI (10-100 mumol/l) had no detectable agonist action but at concentrations of 0.01 and 0.1 mumol/l it acted as an antagonist. Equilibration with the receptors occurred over 2 h. DOI (0.01 mumol/l) depressed 5-hydroxytryptamine but not noradrenaline responses; higher concentrations of DOI also depressed noradrenaline responses.(ABSTRACT TRUNCATED AT 250 WORDS)