Evidence for a dopamine interaction with the central respiratory control system in the rat

Respiratory activity was studied in adult rats during light halothane anesthesia. Dopamine agonists and antagonists were injected intracerebroventricularly (i.c.v.) or systemically. The respiratory parameters were recorded after exposure to O2 or to CO2 in O2. Apomorphine (i.c.v. 300 microgram) induced a biphasic response with an initial decrease in respiratory frequency (f) followed by pronounced tachypnoea after 5 min. The changes in tidal volume (VT) showed an inverse pattern. When apomorphine was administered into the fourth ventricle, only the later phase of the biphasic response was observed. Haloperidol (2 mg/kg i.p.) antagonized the apomorphine-induced response in contrast to domperidone (2 mg/kg i.v.), a dopamine receptor blocking agent which does not pass the blood brain barrier. Administered i.c.v., haloperidol as well as domperidone induced a decrease in f while VT was increased. The same response was observed after the presynaptic dopamine receptor agonist 3-PPP, 3-(3-hydroxyphenyl)-N-n-propylpiperidine. Hypercapnea was found to decrease the tachypnea in apomorphine-treated animals. Apomorphine also induced a decrease in blood pressure and heart rate, which was not reversed by haloperidol. It is concluded that there is a centrally located, tonically activated dopamine system involved in respiratory regulation. The predominant effect seems to be of a respiratory stimulating nature. The possible role of presynaptic and different postsynaptic dopamine receptor mechanisms is discussed.