Effects of enkephalin and 5-hydroxytryptamine on solitary tract neurones involved in respiration and respiratory reflexes

Both enkephalin and 5-hydroxytryptamine (5-HT) have been implicated in neural mechanisms underlying the central control of respiration. In view of the role of the nuclei tractus solitarii (NTS) in respiratory regulation, we carried out a study in artificially ventilated, chloralose-anaesthetized cats of the effects of the microiontophoretic application of [D-Ala2, Met5]-enkephalinamide (DAME) and 5-HT on functionally identified NTS neurones implicated in the control of respiration and respiratory tract reflexes. The neurones examined belonged primarily to two groups: respiratory neurones having a rhythmic activity in phase with the simultaneously recorded phrenic nerve rhythm (viz inspiratory neurones), and presumed reflex interneurones which had no rhythmic activity but which could be orthodromically excited by vagus nerve (X) or superior laryngeal nerve (SLN) stimulation. Application of DAME produced a slow, prolonged depression in 9 of 20 respiratory neurones and 4 of 5 reflex interneurones tested: the remaining neurones showed no change in activity with DAME. The DAME-induced depression was reversed by the intravenous administration of naloxone in the 4 neurones tested. The predominant effect of 5-HT on the 26 respiratory neurones examined was a facilitatory effect of slow onset and long duration; this was noted in 15 neurones. A small number (n = 2) showed a prolonged depression, and the remaining 9 were unaffected. With the reflex interneurones, in contrast, facilitation was not seen with the application of 5-HT; instead, 4 were depressed and 4 unaffected. These findings on functionally identified NTS neurones provide support for the view that both endogenous 5-HT and opiate-related mechanisms are involved in the control of respiration and respiratory tract reflexes. Our findings suggest that they may operate, at least in part, by differing modulatory actions on neurones in the NTS involved in these respiratory-related functions, with enkephalin exerting depressive actions and 5-HT having both facilitatory and depressive effects.