EFFECTS OF CHOUNOCEPTOR ANTAGONISTS ON THE SUCKLING‐INDUCED AND EXPERIMENTALLY EVOKED RELEASE OF OXYTOCIN

Abstract

1 In the anaesthetized lactating rat, the suckling of the young causes the regular release (about every 7 min) of brief pulses of oxytocin (0.5 to 1.0 mu), which each produce a single transient increase in intramammary pressure. 2 The effects of several cholinoceptor antagonists were studied in relation to this natural reflex, and also the release of oxytocin evoked by the intraventricular injection of cholinomimetics. 3 Reflex milk ejection was blocked by the nicotinic antagonists mecamylamine and hexamethonium, and the inhibition was dose-dependent (ED₅₀ of 1 mg/kg i.v. and 5 mg/kg i.v., respectively). Despite the use of high doses, the muscarinic antagonists atropine (200 mg/kg), hyoscine (90 mg/kg) and benzhexol (30 mg/kg) all failed to prevent the reflex release of oxytocin. 4 Acetylcholine (20 to 100 ug), bethanechol (0.2 to 4.0 ug) and carbachol (0.01 to 0.2 ug) injected into the cerebral ventricals stimulated a sustained release of oxytocin, which produced multiple increases in intramammary pressure. Nicotine (200 ug) was relatively ineffective by this route. 5 The release of oxytocin by intraventricular bethanechol or carbachol was abolished by atropine (0.1 to 1.0 mg/kg) but not by mecamylamine (5 mg/kg) or hexamethonium (5 mg/kg). 6 None of the antagonists used significantly affected either the release of oxytocin following electrical stimulation of the neurohypophysis or the mammary sensitivity to endogenous or exogenous oxytocin. 7 The results suggest that the neural pathway controlling the reflex release of oxytocin during suckling in the rat contains a cholinergic component, which acts through nicotinic receptors. A second cholinergic pathway, of the muscarinic type, may also exist. The role of these two pathways is discussed.