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PubMed1986

Blood pressure responses to milk ejection in the young rat.

When young rats receive milk ejections from their mothers they exhibit abrupt 30-50% increases in blood pressure. In our first experiment, we recorded, via carotid cannulae, blood pressure and heart rate during natural nursing bouts. Blood pressure changes coincident with behaviorally defined milk ejections were twice as large as the changes associated with other behaviors observed. In addition, the increases in blood pressure during milk ejection were significantly greater when pups were separated from their mothers for 18-20 hours prior to testing. A second experiment showed that these responses were independent of the mother's overt behavior because virtually identical results were obtained when pups received milk from anesthetized dams stimulated to release milk with oxytocin. These results are discussed with regard to possible immediate functions of the response, and long term effects of repeated cardiovascular activation in early development.

Animals↗
PubMed1983

The role of the septum in the control of the milk ejection reflex in the rat: effects of lesions and electrical stimulation.

Experiments were undertaken to determine the role of the septum on the afferent control of the milk ejection reflex in lactating rats. Massive septal lesions were produced by passing radio-frequency current through lesioning electrodes. Intramammary pressure recordings during suckling showed no significant alterations either in the frequency of milk ejections or in their amplitude and time course. Electrophysiological recordings of identified oxytocin-secreting neurones in supraoptic nuclei of septal-lesioned rats engaged in suckling showed that the pattern of background electrical activity and of the high frequency discharges at milk ejection were normal. The weight of litters from rats lesioned on the third day post-partum increased in a way parallel to that of control litters up to the fifteenth post-natal day. Electrical stimulation was applied bilaterally to the lateral septum in trains of long duration (20-55 min) at varying frequencies. Frequencies of 5 and 10 Hz interrupted the reflex during the period of stimulation. At 1 Hz, milk ejections were not interrupted but the intervals between successive milk ejections were significantly increased in comparison to the intervals before stimulation. Electrical stimulation applied to the septum in short trains of 1 or 3 min at 5 and 10 Hz significantly delayed the appearance of the subsequent milk ejection. At 1 Hz, no effect was observed. Septal stimulation at 1 Hz for 20 min or more did not significantly alter the electrocorticogram during the period of stimulation. Stimulation at 5 Hz for the same period of time always desynchronized the e.e.g. for several minutes after the cessation of stimulation. It is concluded that the septum is not essential for the onset and the maintenance of reflex milk ejections during lactation. The results suggest, however, that in the normal non-anaesthetized animal, septal activation could modulate the frequency of milk ejections.

Action Potentials↗
PubMed1986

Changing characteristics of the milk-ejection reflex during pregnancy, lactation and after weaning in the rat.

The pattern of reflex milk ejection during suckling was investigated in anaesthetized Wistar rats at various stages of pregnancy, lactation and after weaning. Milk-ejection responses were measured using intramammary pressure recordings, and the amount of oxytocin released was estimated from log dose-response lines compiled from the mammary responses to exogenous oxytocin. The number of rats showing intramammary pressure responses to oxytocin increased on Day 22 of pregnancy (the day of parturition) and decreased at 8 days after weaning. The dose-response lines from pregnant animals were shallow, but steepened and shifted to the left during lactation and after weaning. Reflex milk-ejection responses during suckling were detectable in primigravid animals, indicating that birth of the litter and previous suckling experience are unnecessary for the immediate functioning of the reflex. Reflex milk-ejection responses improved during early lactation (such that the frequency and the amount of oxytocin released at each response were maximal at Day 10 of lactation), and subsequently declined in late lactation. Although the frequency of responses in animals 2 and 4 days after weaning was similar to that in late lactating animals, the amount of oxytocin released at each response had risen again to mid-lactation values. In animals undergoing a second pregnancy and lactation the pattern of change in the milk-ejection responses was similar to that of primiparous animals.

Animals↗
PubMed1983

Current concepts on the role of oxytocin in milk ejection.

Timing of oxytocin release may influence milk ejection. Oxytocin is higher in cows after manual premilking stimulation than in cows receiving no stimulation. Premilking stimulation offers no advantages to milk production in short trials but results in shorter times of machine on and higher average rate of milk flow. Enhanced mechanical stimulation does not seem as effective as manual stimulation in short trials. Oxytocin release is multiphasic, and contents in blood decline during milking. Maximal concentrations during milking decrease across lactation. Nonlactating cows also release oxytocin upon udder stimulation and conditioning. Virgin heifers do not respond in the same way to udder stimulation as lactating cows, thus suggesting that sensitivity of the milk ejection reflex depends upon the physiological state of the animal. Cows probably release about one-third of their stores of oxytocin at milking, and it appears that little hormone is necessary for effect at the udder. Basal concentrations of oxytocin decrease from early to midlactation and increase from mid to late lactation and from late lactation to involution. Half-lives, metabolic clearance rates, and entry rates for oxytocin were measured in cattle in various physiological states. Data from these measurements are discussed.

Animals↗
PubMed1995

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

1. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central administration of a GABAA receptor agonist (muscimol) and antagonist (bicuculline) on the milk ejection reflex in the urethane-anaesthetized rat. 2. Intracerebroventricular (i.c.v.) injection of both muscimol (n = 17), at doses of 5, 10 and 20 ng, and bicuculline (n = 15), at doses of 0.01, 0.1 and 0.3 microgram, inhibited the milk ejection reflex in a dose-dependent manner. The bicuculline-induced inhibition was accompanied by desynchronization of the electroencephalogram and, at the highest dose, by alteration in the sensitivity of the mammary gland to oxytocin. No significant effect on the milk ejection reflex was seen with i.c.v. isotonic saline (n = 5). 3. Injection of 20 (n = 5) or 40 ng (n = 2) muscimol or 0.1 microgram bicuculline (n = 5) i.c.v. did not significantly alter the rise in intramammary pressure evoked by electrical stimulation of the neurohypophysis. 4. Bilateral 400 nl microinfusions directly into the supraoptic nuclei of either muscimol (20-100 ng microliter(-1); n = 10) or bicuculline (0.15 micrograms microliter(-1); n = 5) [corrected] resulted in an inhibition of the milk ejection reflex, which was not accompanied by desynchronization of the electroencephalogram. 5. The effects of i.c.v. injections of muscimol (15 and 20 ng) and bicuculline (0.01, 0.12 and 0.3 microgram) on the electrical activity of twenty-seven antidromically identified supraoptic magnocellular neurones were examined. Both compounds resulted in an inhibition of the background firing of oxytocinergic and vasopressinergic cells, and delayed the occurrence of high frequency bursts in oxytocin neurones. In five supraoptic neurones, bicuculline induced a transient activation before inhibition. 6. The powerful inhibitory action on the milk ejection reflex of both muscimol and bicuculline provides evidence for the importance of GABA neurones in maintaining the functional integrity of the mechanisms which allow the intermittent and pulsatile release of oxytocin during suckling.

Action Potentials↗
PubMed1984

Participation of the hippocampus in the facilitatory effect of an exteroceptive stimulus on milk ejection.

The auditory exteroceptive stimulus emanating from a lactating rat and the litter while suckling was used to facilitate milk ejection in another "induced" mother suckled by her own litter. Sectioning of the tractus corticohypothalamicus medialis (TCM) or the columns of the fornix, prevented the facilitatory effect of the exteroceptive stimulus on milk ejection. Sham operated induced mothers gave significantly more milk than noninduced rats. Electrolytic lesioning of the stria terminalis did not affect normal milk ejection nor the response to the exteroceptive stimulus. It is proposed that the hippocampus through the TCM may facilitate the suckling-induced milk ejection when an appropiate exteroceptive stimulus is applied. Neither the lesion of the stria terminalis nor the section of the fornix or the TCM seems to alter the normal suckling-induced milk ejection. A general modulatory role of the limbic system is described.

Animals↗
PubMed1985

Evidence for a spinal site at which opioids may act to inhibit the milk-ejection reflex.

Morphine was injected into the lumbar subarachnoid space of anaesthetized lactating rats (7-10 days post partum) to examine its effect on the milk-ejection reflex at a spinal level. Although the delay until the first milk-ejection response to the suckling of hungry pups was variable (3-60 min) the subsequent responses occurred at regular intervals of 7.5 +/- 0.4 min; milk-ejection responses were detected by measurement of intramammary pressure and by the characteristic behaviour of the pups. Injection of morphine (4-50 micrograms) via a cannula inserted into the spinal subarachnoid space inhibited reflex milk ejection in a dose-related manner without affecting the sensitivity of the mammary gland to exogenous oxytocin (1 mu., i.v.); injection extradurally was without effect. The opiate antagonist naloxone (10 micrograms), when injected intrathecally, did not significantly alter the pattern of reflex milk ejection or the amplitude of the intramammary pressure response, but prevented the inhibitory effect of morphine when administered with the opiate. Pethidine (250 and 400 micrograms) also inhibited the milk-ejection reflex. It is unlikely that the effect of spinal administration of morphine occurred as the result of the transportation to a supraspinal site since release of oxytocin evoked by intraventricular injection of hypertonic sodium chloride (3 mol/l) was blocked by intraventricular injection of morphine (4 micrograms) but not by a much larger dose (40 micrograms) injected intrathecally.

Animals↗
PubMed1985

Reappraisal of the influence of mammary distension on the frequency of milk ejection in the rat.

Experiments were performed to reinvestigate the importance of mammary engorgement for activation of the milk-ejection reflex in the rat. Reflex milk ejection (measured by intramammary pressure recordings during a 2-h suckling test under anaesthesia) was compared in rats with engorged mammary glands (15-h separation from the pups, followed by sham-removal of milk) and in rats with drained mammary glands (15-h separation, followed by milk removal using a foster litter and exogenous oxytocin). In experiment 1, multiple small (2 mu.) doses of oxytocin were used for milk removal: these were effective in emptying the mammary glands and caused no subsequent impairment or change in sensitivity of the mammary response to oxytocin. Using this draining procedure, no significant differences were observed in either the number or relative amplitude of the milk ejections, or the occurrence of pup stretch reactions between engorged and drained rats. Similar results were seen in experiment 2, where an identical draining protocol was used, but the rats were pretreated with propranolol before the suckling test. In experiment 3, large (250 mu.) oxytocin doses were used for milk removal, as in previous studies. Again mammary draining had no effect on milk ejection in a subsequent suckling test (with propranolol pretreatment). However, the number of stretch reactions shown by the pups was significantly (P less than 0.001) reduced from 8.6 +/- 1.4/2 h to 1.9 +/- 0.6/2 h. This effect probably related to long-term impairment of the oxytocin response of the mammary glands following the draining procedure, and could not be attributed to the draining per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Effect of L-dopa on milk ejection and prolactin release in lactating rats.

The effect of L-DOPA on milk ejection and on prolactin release during 30 min of suckling was studied in lactating rats. Various doses of L-DOPA (1-25, 2-5, 5 and 10 mg/100 g body wt) were injected i.p. 30 min before the suckling period. Control rats were injected with 0-9% NaCl solution only. An inhibition of milk ejection proportional to the dose of drug administered was obtained. The dose of 10 mg completely blocked milk ejection but 1-25 mg had no effect. A normal milk-ejection response was obtained with a small dose of oxytocin injected immediately before nursing into mothers treated with 10 mg L-DOPA, indicating that the blocking effect was not due to a lack of mammary gland response. In control mothers, serum prolactin levels increased from 67-2 +/- 25-9 (S.E.M.) to 950-3 +/- 118-7 ng/ml after a 30 min suckling period. L-DOPA (5 and 10 mg) prevented the release of prolactin induced by suckling, but 1-25 and 2-5 mg L-DOPA had no effect. The results indicate that oxytocin and prolactin release induced by suckling in lactating rats is inhibited by an increase of catecholamines at the hypothalamic-hypophysial axis.

Animals↗
PubMed1984

Stimulation of milk secretion with inhibition of milk ejection by corticosteroids during extended lactation in the rat.

Milk yield declined significantly between days 22 and 28 of lactation in rats, when lactation was extended by frequent replacement of older litters with younger ones. Corticosterone implants but not cortisol injections or implants prevented this decline. Cortisol, however, appeared to inhibit milk ejection since the mammary glands became engorged with milk and milk yield was improved dramatically by oxytocin injections. In both cases corticosteroid concentrations increased approximately threefold above basal concentrations. Both corticosteroids increased total mammary gland RNA content and lipoprotein lipase (LPL) activity of the mammary gland but were without effect on insulin binding. They also decreased LPL activity, lipogenesis and the number of insulin receptors on adipose tissue. Serum prolactin and insulin concentrations were unaffected by any of the treatments. The results suggest that corticosteroids inhibit milk ejection under certain conditions, may be circulating in lower concentrations, which thereby limit milk production, during prolonged lactation and may improve milk yield during extended lactation in part by suppressing anabolic activity in adipose tissue.

Adipose Tissue↗
PubMed2004

Changes in cisternal compartment based on stage of lactation and time since milk ejection in the udder of dairy cows.

Two experiments were conducted to study changes induced by stage of lactation and milk ejection in the cisternal compartment of the udder in dairy cows. In experiment 1, 18 cows grouped according to stage of lactation were used 12 h after milking for measuring alveolar and cisternal milk volumes (by cannula) and cisternal area (by ultrasonography) in the front quarters. Cisternal milk and cisternal area were correlated (r = 0.74 to 0.82) for all stages of lactation. As lactation advanced, volumes of alveolar and cisternal milk and cisternal area decreased. Proportion of cisternal milk varied between stages (early, 33.2%; mid, 23.1%; and late, 42.6%). In experiment 2, 7 cows were used to show return of milk from cisternal to alveolar compartments when milk ejection was induced without milking. Cisternal area was measured before (0 min) and after (3, 15, 30, and 60 min) an i.v. oxytocin (OT) injection administered immediately before normal a.m. and p.m. milking times. Cisternal area increased dramatically from 0 to 3 min (98%) and decreased slowly thereafter. The 0- and 3-min data provide clear evidence of milk ejection, and their difference indicated cistern elasticity. Maximum cisternal area in each cow was similar for the 8- and 16-h milking intervals, indicating that in both cases the cistern was completely full of milk. Decrease in cisternal area after 3 min was significant at 15, 30, and 60 min. Decreased cisternal area was interpreted as the reflux of cisternal milk to the alveolar compartment. We termed this 'cisternal recoil.' In conclusion, ultrasonography was a useful method to evaluate dynamic changes in cisternal milk throughout lactation and after udder stimulation in dairy cows. Evidence exists that udder cisterns decrease when lactation advances and milk returns to the alveolar compartment when cows remain unmilked after milk ejection.

Animals↗
PubMed1997

Inhibition of milk ejection in cows by oxytocin receptor blockade, alpha-adrenergic receptor stimulation and in unfamiliar surroundings.

Inhibition of milk ejection in cows by oxytocin receptor blockade (Atosiban) and alpha-adrenergic receptor stimulation (phenylephrine) prior to prestimulation was compared with inhibition of milk ejection in unfamiliar surroundings. In addition, Atosiban and phenylephrine were administered after a 1 min prestimulation or 1 min after the start of milking. Oxytocin concentrations increased during milking in all treatments. The spontaneously removed milk fraction (before oxytocin was injected) was similar for Atosiban and phenylephrine treatments and in unfamiliar surroundings, but lower than in controls. Peak flow rates were similar in all treatments, but reduced as compared with controls when phenylephrine and Atosiban were administered before prestimulation. Peripheral (Atosiban, phenylephrine) and central (unfamiliar surroundings) inhibition of milk ejection reduced the amount of available milk similarity. Drug treatments resulted in similar peak flow rates; however, teats were contracted after phenylephrine administration but not after Atosiban. The inhibition induced by Atosiban could be abolished by oxytocin injection, but not induced by phenylephrine, which was antagonized by alpha-adrenergic receptor blockade. These results indicate that inhibition of milk ejection through activation of alpha-adrenergic receptors is based on blockade of milk flow into the cistern, but not through the teats.

Animals↗
PubMed1987

Prolonged electrical stimulation of the nipples evokes intermittent milk ejection in the anaesthetised lactating rat.

Intermittent and continuous electrical stimulation of the nipples elicited milk-ejection responses in the lactating rat. The responses occurred intermittently, with similar amplitudes and periodicity as those seen in suckled rats. The responses were always associated with synchronization of the electroencephalogram (EEG), but some rats with synchronized EEG activity did not milk eject during stimulation. Since continuous stimulation also resulted in intermittent milk ejection it seems unlikely that the periodicity of the reflex in suckled rats depends upon changes in the intensity of sensory stimulation. The techniques of nipple stimulation may be a useful method with which to study neural pathways and other phenomena such as gating involved in oxytocin release and milk ejection. The success of the technique depends on a variety of factors such as parameters of the stimulation and state of anaesthesia.

Anesthesia↗
PubMed1978

Spontaneous milk ejection during lactation and its possible relevance to success of breast-feeding.

In a woman suckling twins it became apparent that both suckling-induced and precisely timed, spontaneous bursts of milk ejection were occurring. Observations on days 14, 28, 56, and 112 of lactation disclosed highly significnat increases in intervals between episodes of spontaneous milk ejection. Furthermore, at all stages of lactation the interval between a feed and the next episode of spontaneous ejection was significantly longer than the interval between spontaneous ejections. The decrease in frequency of episodes of spontaneous milk ejection during lactation may be related to the decreasing release of prolactin in response to suckling. Spontaneous milk-ejection episodes are felt only when the breast is full and may signal its readiness for a further suckling episode. Such bursts of milk ejection may stimulate the suckling response in babies, suggesting that rigid three- or four-hour feeding regimens may be unphysiological and pose a threat to the success of breast-feeding in the early postnatal period.

Breast Feeding↗
PubMed1968

The effect of an exteroceptive stimulus on milk ejection in lactating rats.

1. The exteroceptive stimulus emanating from a lactating rat and the litter while suckling was used to induce milk ejection in another lactating mother 15 min before the replacement of her own litter. The effect of the external stimulus on milk ejection during one 30 min period and four 15 min periods of nursing was studied.2. After being isolated for 9 hr the litter from the mother subjected to the exteroceptive nursing stimulus (induced rat) obtained a significantly greater amount of milk during 30 min of nursing than that obtained by the litter from the control mother.3. When deaf mother rats were used the gain of milk by the litter showed no difference between the control and the induced mother. This result indicated that the effective external stimulus is an auditory one and is probably produced by the mother rat and the young while suckling.4. The administration of oxytocin (Syntocinon, Sandoz) 20 m-u./100 g body wt., 15 min before the replacement of the litter produced a milk ejection similar to that obtained under the influence of the auditory stimulus. This would indicate that the exteroceptive stimulus probably evokes the release of oxytocin from the neurohypophysis.5. When nursing was performed in four periods of 15 min each the litter of the control mother obtained milk only in the second period of nursing while the litter of the induced mother obtained milk in all four periods of nursing and the amount of milk obtained in the whole hour was greater than that from the control rat.6. The administration of oxytocin just before the replacement of the litter every 15 min produced milk ejection only in the first two periods of suckling in the control rats but the induced rats were capable of ejecting milk during all four periods.7. The most satisfactory conclusion for the results obtained is that the C.N.S. regulates both the release of oxytocin in response to suckling and the response of the mammary gland to oxytocin, in the lactating rat.

Animals↗
PubMed1993

Electrical activity of neurons in the ventrolateral septum and bed nuclei of the stria terminalis in suckled rats: statistical analysis gives evidence for sensitivity to oxytocin and for relation to the milk-ejection reflex.

Our previous results obtained by lesioning or stimulating the ventrolateral part of the lateral septum and the bed nuclei of the stria terminalis suggested that this area is involved in the control of milk ejection pattern in rats. The present study was undertaken with the aim of testing ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons as a putative link of the neuronal network controlling the bursting activity of oxytocin neurons in suckled lactating rats (anaesthetized with urethane). Ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons were recorded simultaneously with hypothalamic oxytocin neurons in either the paraventricular or supraoptic nucleus in rats with (n = 26) or without (n = 29) periodic milk ejections. Analysis of their firing pattern enabled differentiation of two subgroups: type I, characterized by numerous high frequency spikes, often grouped in clusters; and type II with very few or no high frequency clusters of spikes. The probability density function of the interspike intervals of both patterns could be modelled using a mixture of two log-normal distributions, the parameters of which differed significantly. The presence of absence of milk ejections did not influence the overall mean level of activity (2.0 +/- 0.5 and 1.9 +/- 0.4 spikes/s, respectively). However, the characteristics of the type I firing pattern were affected by the presence of the milk-ejection reflex. The average level of activity was not always constant and 16/55 ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons displayed cyclical activity (from 0.6 +/- 0.2 to 4.0 +/- 0.5 spikes/s) both in the presence (n = 8) and absence (n = 8) of the milk-ejection reflex. In five of eight neurons recorded during milk-ejection reflex, the cycles in firing were clearly correlated with the bursting of oxytocin neurons. These five neurons exhibited the type I firing pattern. The three remaining neurons and the eight neurons recorded in the absence of milk-ejection reflex displayed the type II firing pattern. Oxytocin (1-2 ng = 0.45-0.9 mU) was injected into the third ventricle (i.c.v.) in order to examine the possible involvement of ventrolateral part of the lateral septum-bed nuclei of the stria terminalis neurons in the facilitatory effect of oxytocin on the reflex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Intramammary pressure in the lactating sow in response to oxytocin and during natural milk ejections throughout lactation.

We developed a simple, non-invasive method to measure the intramammary pressure (IMP) response in sows during natural milk ejection and after i.v. injections of oxytocin. The teats of sows were cannulated and the amplitude and duration of IMP changes were measured via a pressure transducer linked to a computer. During natural milk ejections, the amplitude of the response was 5.5+/-1.8 kPa (mean +/- SD) and the duration of response at half the peak amplitude was 6.8+/-1.6 s. In response to oxytocin a threshold response occurred at 60 mIU oxytocin with no further change up to 200 mIU. The amplitude of the response to an i.v. dose of 60-200 mIU oxytocin (5.5+/-2.2 kPa) and duration (6.4+/-1.7 s) were similar to that during a natural milk ejection. The responses of two galactophorous ducts of a teat measured simultaneously were similar in peak amplitude and duration. When the responses of four glands of a sow were measured simultaneously, there was a lag time in the onset of the IMP peak from the anterior to the posterior glands, and an increase in the peak amplitude from anterior to posterior. Both during natural milk ejections and in response to oxytocin injections, there were significant differences in peak amplitude between sows. We also aimed to determine whether the pressure or duration of milk flow during natural milk ejections was limiting piglet growth rates. IMP of nine sows and the growth rates of their piglets were measured. Both the peak amplitude of IMP response and the growth rate of piglets increased over the course of lactation, but the relationship was not causal. We found that the growth rate of piglets did not depend on IMP amplitude or duration, but we suggest that it may depend on the frequency of suckling and/or the ability of piglets to withdraw milk while it is available.

Animals↗
PubMed1990

Facilitatory effect of hypothalamo-neurohypophysial tract stimulation on milk ejection frequency in the lactating rat.

The relative contribution of magnocellular and parvocellular neurones to the patterning of milk ejections was studied by activation of various parts of the hypothalamo-neurohypophysial tract. During suckling of anaesthetised lactating rats, electrical stimulation of the neurohypophysis/neural stalk (15 Hz, 1.5 s on/1.5 s off, 10 min) evoked an increased frequency of milk ejections as detected by intramammary pressure recording. Bilateral stimulation of the paraventricular nuclei produced a similar facilitation in the post-stimulus period, but stimulation of the supraoptic nuclei (with either low current or current sufficient to evoke peripheral oxytocin release) had no effect on the occurrence of milk ejections. These data are consistent with the hypothesis that parvocellular but not magnocellular neurones participate in the regulation of milk ejection frequency.

Animals↗