SUMMARY Milk ejection (ME) was studied in the lactating rat by the measurement of intramammary pressure, milk yield and behaviour. An intermittent pattern of ME was observed, both in conscious rats and in rats anaesthetized with tribromoethanol, pentobarbitone sodium and ethyl carbamate. Milk ejection was never seen as a reflex response with the onset of the suckling stimulus; the latency to the first ME varied from 10 min in the conscious rat to > 60 min during deep anaesthesia. Thereafter, ME occurred at regular intervals ranging from 3 to 5 min under optimal conditions to > 15 min during less favourable circumstances, though the young were content to suckle continuously for several hours irrespective of whether they obtained milk. Each ME was associated with an abrupt and uniform rise in intramammary pressure and simulation of the individual ME was obtained by a rapid i.v. injection of 1 mu. oxytocin. The pups reacted immediately to the rise in pressure with a synchronized extensor reaction and a vigorous increase in suckling which lasted for about 10 s. There was, however, no apparent change in the suckling stimulus to account for the release of endogenous oxytocin some 10–20 s prior to these events. Milk ejection was a reflex phenomenon, nonetheless, for the removal of the pups abolished the intermittent release of oxytocin. The rise in intramammary pressure was associated directly with the ejection of the milk and the pups abruptly increased in weight. Yields of 10–12 g were obtained from both conscious and anaesthetized rats after 18 h of separation from their young. Most of this milk was expressed in the first ten milk ejections. Mammary distension and the size of the litter were important parameters determining the pattern of ME. The incidence of ME was appreciably lower in unseparated rats whether anaesthetized or not and in separated rats after prolonged suckling or artificial removal of the milk. A similar reduction was encountered when the number of suckling pups was changed from ten to five. The physiological principles of the ME reflex in the rat are discussed and a theoretical model is presented.

SUMMARY Antidromically-identified paraventricular (PV) neurones were studied in the anaesthetized rat during milk ejection (ME) evoked by the natural stimulus provided by the suckling young. An intermittent pattern of ME was observed, though the ME interval was slightly longer (10–20 min) in the doe during unit recording than in unoperated or conscious animals (5–15 min). PV neurones displayed a steady background of spike discharge in both the non-lactating rat and lactating rat during suckling. The firing rates ranged from 0 to 9·4 spikes/s and were exponentially distributed with 32% of the units firing at <1 spike/s. Phasic patterns of discharge were seen in 18% of the units. Fifty-eight per cent of the PV units displayed a stereotyped and explosive acceleration in spike activity some 15–20 s before the rise in intramammary pressure at ME. The peak firing rate during this brief (2–4 s) response was in the range of 24–84 spikes/s. A prominent after-inhibition was then displayed by these responsive units, though this second component of the response was variable in duration (7–56 s). The electrical activity of the remaining units, including all the cells with phasic discharge, was not correlated with ME. There was no apparent change in the intensity of the suckling stimulus at the time of PV activation, i.e. 15–20 s before ME. Secondly, the activity of the PV neurones was not influenced by the rise in the intramammary pressure and the increased sucking of the pups at the time of ME. Simulation of an individual ME was obtained with both 1 mu. exogenous oxytocin, i.v., and electrical stimulation of the neurohypophysis (50 pulses/s for 4 s). The latencies to ME ranged from 7–14 s and 11–23 s, respectively. In conclusion, an explosive increase in the electrical activity of PV neurones precipitates the release of oxytocin at ME.

SUMMARY1. Antidromically identified supraoptic (SO) units were recorded in lactating rats anaesthetized with urethane (1.1 g/kg), and their activity was studied during milk ejection evoked by the suckling of the young. Fifty-eight SO units were recorded through 174 milk ejections. Each milk ejection was the result of a neurohypophysial release of an oxytocin pulse of 0.5-1-5 m-u.2. Fifty-five of the SO units displayed background activity and three were silent. The firing rates ranged from 0 to 15-4 spikes/sec, the distribution was exponential with 26 % of the units firing at < 1 spike/sec. Sixteen (28 %) of the SO units displayed a phasic pattern of activity characterized by periods of activity (6-132 sec) and silence (4-71 sec).3. Twenty-five of the non-phasic units displayed a large and stereotyped acceleration in spike activity some 10-5-17-4 see before the rise in intramammary pressure at milk ejection. Units accelerated to rates between 9-66 spikes/sec, an increase of about thirtyfold (median) on background activity. The response was brief (0.9-4.7 see) and was followed by a period of after-inhibition.4. It was concluded from studies of double recordings and observations of multi-unit activity that all the responsive units were synchronously activated. The mean latency of 13-3 sec between the onset of the neurosecretory response and milk ejection was similar to that observed following the experimental release of endogenous oxytocin by electrical stimulation of the neurohypophysis (50 pulses/sec for 2-4 sec).5. Four of the phasically active units were correlated with the oxytocin release for milk ejection. Three of these units displayed a burst of activity superimposed on the terminal portion ofan active phase, some 10 2-14*7 see

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SUMMARY1. Lactating rats were implanted with a cannula in a lateral cerebral ventricle to deliver morphine (up to 50 jtg/h) chronically from a subcutaneous osmotically driven mini-pump. After infusion of morphine for 5 days the rats were anaesthetized with urethane and prepared with ventral surgery for recording the electrical activity of single, antidromically identified neurones in the supraoptic nucleus.2. A single i.v. injection of naloxone (5 mg/kg) in these rats provoked a longlasting, large increase in intramammary pressure, but in control rats had negligible effects. Concentrations in plasma of oxytocin, measured by radioimmunoassay in samples of femoral arterial blood, rose from 44-7 + 2-5 to 1072 1 + 89-5 pg/ml (means+s.E.M.) 6 min after naloxone in the morphine-treated rats. In control rats, the concentration of oxytocin in plasma rose only from 42-1 + 2-9 to 125-1 + 28-2 pg/ml after naloxone.3. Naloxone produced a transient increase in arterial blood pressure in morphinetreated but not control rats. Concentrations in plasma of vasopressin, measured by radioimmunoassay in samples of femoral arterial blood, rose in morphine-treated rats from 7-4 + 2-4 to 29-2 + 3-7 pg/ml after naloxone, but did not rise significantly in control rats.4. Naloxone (1-5 mg/kg) produced a prompt and prolonged increase in the discharge rate of each of ten continuously active (putative oxytocin) cells recorded from ten morphine-treated rats. The discharge rate of the six cells tested at the highest dose (5 mg/kg) increased by an average of 6-3 Hz (360 %) within 5 min, and the firing rate remained elevated for at least 30 min; the discharge rate of six continuously active supraoptic neurones recorded in control rats was not affected by naloxone.5. The firing activity of five phasic (putative vasopressin) supraoptic neurones in morphine-treated rats was increased for at least 30 min by the injection of naloxone; these increases were the result of a raised intraburst firing rate with no change in burst duration or frequency. One phasic neurone was inhibited for 15 min, and one phasic neurone was unaffected. R. J. BICKNELL AND OTHERS 6. The excitatory effects of naloxone on neurones in the supraoptic nucleus of morphine-treated rats were not explained by changes in blood pressure or osmolarity and did not depend on suckling or a cholinergic pathway.7. The concentrations of oxytocin in plasma and the operation of the milk-ejection reflex were similar in the controls and morphine-treated rats, prior to naloxone. These findings indicate tolerance to initial inhibitory effects of morphine on oxytocin secretion. Likewise, before naloxone the concentrations of vasopressin in plasma and firing activity of phasic neurones were similar in the morphine-treated and control groups, indicating tolerance to any effects of morphine on vasopressin neurones.8. The uniform excitation of continuous neurones, accompanied by massive secretion of oxytocin provoked by naloxone in the morphine-treated rats, indicates dependence on morphine in the centra...