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. 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.

Central inhibitory effects of muscimol and bicuculline on the milk ejection reflex in the anaesthetized rat.

“…injection of the vehicle alone did not modify the pattern of the reflex in any animal of the control group (n = 5), nor the EEG activity in the three rats in which it was recorded (Fig. 1A); the mean milk ejection ratio was equal to 1t1 + 0 1 (the milk ejection ratio as defined by Clarke et al (1978) is the duration of the longest interval between milk ejections following drug injection divided by the mean interval before treatment). The GABAA receptor agonist muscimol at 5, 10 and 20 ng inhibited the milk ejection reflex in 2/5, 4/5 and 7/7 animals, respectively ( Fig.…”

“…The source of GABAergic innervation to the supraoptic nucleus has not been fully investigated but is believed to come at least in part from the perinuclear zone of the supraoptic nucleus (Roland & Sawchenko, 1993 (Mason, Poulain & Cobbett, 1987;Randle & Renaud, 1987). Furthermore, evidence of frequent spontaneous GABAmediated inhibitory postsynaptic potentials in supraoptic neurones (Randle, Bourque & Renaud, 1986;Wuarin & Dudek, 1993) (Isherwood & Cross, 1980 Clarke et al (1978), and by calculating the milk ejection ratio.…”

Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment.

“…carbachol can elicit comparable intramammary pressure responses to those seen in the present experiments with naloxone (Clarke, Fall, Lincoln & Merrick, 1978;Rayner et al 1988), we attempted to determine whether the same pathway is involved by administering i.v. atropine (2x5 mg/kg), which blocks the carbachol-induced response.…”

Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones.

“…morphine) and as a control procedure in vehicle-infused rats; mammary gland sensitivity to exogenous oxytocin was retested 30 min later (range 17-44 min). In some rats a second injection of naloxone was given 60 min after the first; and, or, 80 min (range 34-110 min) after the first injection of naloxone an injection of carbachol (carbarnylcholine chloride, 0 2 jug in 1 #u1 saline, Sigma Chemical Co.) was given via the guide cannula into the left lateral cerebral ventricle with a microsyringe, to stimulate oxytocin secretion (Clarke, Fall, Lincoln & Merrick, 1978).…”