Dopaminergic control of oxytocin release in lactating rats.

During suckling, anaesthetized lactating rats release regular (about every 7 min) but brief pulses of oxytocin (0.5--1.0 mu.) which produce single transient increases in intramammary pressure. Drugs which selectively impair synaptic transmission were used to determine the role of dopamine and noradrenaline in regulating this natural reflex. Diethyldithiocarbamate (100--200 mg/kg, i.v.) and alpha-methylparatyrosine (100--400 mg/kg, i.v.) which inhibit the synthesis of catecholamines both blocked the suckling-induced release of oxytocin. The milk-ejection reflex was also inhibited in a dose-dependent manner by the intravenous administration of the dopamine antagonists, fluphenazine (0.7 mg/kg), pimozide (1.4 mg/kg), cis-dupenthixol (4.5 mg/kg) and metoclopramide (6.0 mg/kg), and caused a significant inhibition P less than 0.01) of the reflex in 50% of the rats tested. The alpha-adrenoceptor antagonist phenoxybenzamine (1.4 mg/kg) was similarly effective. Dopamine (40 micrograms), bromocriptine (10 micrograms), apomorphine (100 micrograms), noradrenaline (10 micrograms) and phenylephrine (2 micrograms) injected into the cerebral ventricles evoked a sustained release of oxytocin which produced multiple increases in intramammary pressure; isoprenaline (4 micrograms) was ineffective. The release of oxytocin evoked by dopamine and noradrenaline was prevented by cis-flupenthixol and phenoxygenzamine respectively. None of the drugs used affected the mammary sensitivity to exogenous oxytocin nor were their actions modified by pretreatment with propranolol (1 mg/kg). The results suggest that the neural pathway for the reflex release of oxytocin during suckling in the rat contains both dopaminergic and noradrenergic synapses, the latter acting through alpha-adrenoceptors and being distal in the pathway to the dopaminergic component.