A possible dopaminergic pathway mediating hypoxic depression in neonatal rabbits.
Previous studies show a differential effect of dopamine and its agonist apomorphine on ventilation, being depressant on adults and stimulatory on fetal respiratory breathing movements. In view of this we studied the effect of apomorphine, specific antagonists of dopamine receptors SCH 23390 (D1), sulpiride and domperidone (D2), and cis(z)-flupentixol (D1 + D2) on the typical ventilatory response to hypoxia in neonatal rabbit pups. This ventilatory response to hypoxia is characterized by an initial stimulatory (phase 1) followed by a declining (phase 2) pattern. Cis(z)-flupentixol markedly increased phase 1 and abolished phase 2. A similar effect was seen with SCH 23390. Administration of sulpiride or domperidone increased phase 1 but did not affect phase 2, thereby not altering the biphasic pattern of ventilation to hypoxia. The abolition of the biphasic response in neonatal pups on decerebration was also found to be restored by topical application of apomorphine in the fourth ventricle. Our results suggest that dopamine is acting centrally in mediating the declining phase of the biphasic response to hypoxia in rabbit pups possibly via the D1-receptors.
Srinivasan
M
M
Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm, Sweden.
Lagercrantz
H
H
Yamamoto
Y
Y
D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003655:Decerebrate State; D004294:Domperidone / Q000494:pharmacology; D018492:Dopamine Antagonists; D005475:Flupenthixol / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004294:Domperidone; D013469:Sulpiride; D005475:Flupenthixol; D001058:Apomorphine