Effects of neurotoxin-induced brainstem lesions on the respiratory responses of conscious rats.

Respiration was recorded in unanaesthetized rats breathing air, or CO2 in air, 4-8 days after injection into the rostral brainstem at the level of the dorsal raphe nucleus of either a catecholaminergic neurotoxin, a serotoninergic neurotoxin, or the vehicle (0.5% ascorbic acid) of these drugs. Some rats were pretreated with the noradrenergic neurone protecting agent, desmethylimipramine (DMI). Vehicle injection resulted in an increase in the frequency (f) sensitivity to CO2. In two of four cases, injection of 6-hydroxydopamine caused a similar response but in the remaining cases injections caused increases in inspiratory duration (TI), expiratory duration (TE) and tidal volume (VT) during air-breathing. The serotonergic neurotoxin, 5,7-dihydroxytryptamine, reduced the frequency sensitivity to CO2 significantly. This reduction was not sustained. In all cases air-breathing f was decreased due to a prolongation of TI; in most cases air-breathing VT was increased. The characteristic effect of midline 5,7-dihydroxytryptamine lesions was an increase in the VT sensitivity to CO2. On the basis of the results, it is proposed that noradrenaline is essential to the processes determining basic respiratory rhythm, whereas dopamine and serotonin are important inhibitors in chemoreflex ventilatory patterns.