NEUROHORMONAL MECHANISMS IN EMOTIONAL INHIBITION OF MILK EJECTION

1955 ◽  
Vol 12 (1) ◽  
pp. 29-37 ◽  
Author(s):  
B. A. CROSS

SUMMARY 1. Fifteen lactating rabbits were maintained on a regime of one daily nursing in which litter weights, milk yields and duration of nursing were recorded. 2. Sodium pentobarbitone anaesthesia blocked the milk-ejection reflex and prevented the removal of more than 15% of the full milk yield by the young. Intravenous injection of 50 mU oxytocin regularly restored normal milk removal; 10 and 20 mU did not. 3. In thirty-five out of forty-two experiments in which the does were suckled while under forcible restraint the amount of milk removed was reduced by 20–100%. In twenty-nine cases injection of 50 mU oxytocin restored normal milk removal. In the remaining six experiments this replacement therapy was fully effective only after the does had been anaesthetized. 4. Kymograph records of milk-ejection responses showed that normal milk removal was associated with a reflex milk-ejection response similar to that produced by 50 mU oxytocin, and incomplete milk removal with a reduced (=5 mU oxytocin) or absent milk-ejection response. Where injection of 50 mU oxytocin failed to restore normal milk removal in the conscious animal, the resulting milk-ejection response was reduced by an amount similar to that produced by injection of 1μg adrenaline. 5. The results indicate that, while activation of the sympathetico-adrenal system does occur, the main factor in emotional disturbance of the milk-ejection reflex is a partial or complete inhibition of oxytocin release from the posterior pituitary gland.

1953 ◽  
Vol 9 (1) ◽  
pp. 7-18 ◽  
Author(s):  
B. A. CROSS

1. Emotional inhibition of the milk-ejection reflex in rabbits is described. 2. Injection of 5–50 μg adrenaline intravenously into does before nursing interfered with milk ejection, as shown by the failure of the young to withdraw more than three-quarters of the normal yield of milk. Injection of 150 mU (=milliunits) 'Pitocin' immediately after the adrenaline did not restore normal milk ejection. 3. Intravenous injection of 5 μg adrenaline suppressed the milk-ejection response to 50 mU posterior pituitary extract in anaesthetized rabbits with cannulated teats, provided the injection of adrenaline preceded that of the posterior pituitary extract. The inhibitory effect had not entirely disappeared in 2 min. 50μg adrenaline prevented the occurrence of milk ejection for 3½ min. 4. Intravenous doses of 5 μg adrenaline, but not smaller amounts, inhibited the milk-ejection response to electrical stimulation of the supraoptico-hypophysial tract, if injected before stimulation or during the latent period of the response. When injected after the commencement of milk ejection 5 μg adrenaline was without effect, but 50 μg abolished the response. 5. Electrical stimulation of the posterior hypothalamus produced inhibition of the milk-ejection response to injected oxytocic extract, together with pupillary dilatation and exophthalmos. The inhibition closely resembled that resulting from injection of adrenaline. 6. It is concluded that one mechanism involved in the emotional inhibition of milk ejection is an activation of the sympathetico-adrenal system, resulting in antagonism of the action of the neurohypophysial milk-ejection hormone on the contraction process within the mammary gland.


1981 ◽  
Vol 91 (2) ◽  
pp. 233-244 ◽  
Author(s):  
T. S. JUSS ◽  
J. B. WAKERLEY

Experiments were performed on anaesthetized lactating rats to investigate the effects of radiofrequency lesions of the mesencephalon on the milk-ejection reflex. In lesioned and control rats, intramammary pressure recordings were used to estimate oxytocin release (number and relative amplitude of the intermittent milk-ejection responses) during a 3-h suckling test with ten pups. Bilateral lesions (diameter 0·5–1·5 mm) of the lateral tegmentum (near the brachium of the inferior colliculus and medial geniculate body) seriously disrupted the milk-ejection reflex, reducing the number of rats ejecting milk (two out of ten v. all 12 controls, P<0·001) and the amount of oxytocin they released (1·35±0·35 (s.e.m.) v. 15·52±2·19 mu. for controls, P<0·05). Unilateral lesions of the lateral tegmentum also impaired milk ejection and, if the suckling stimulus was restricted only to the contralateral nipples, oxytocin release was virtually abolished. Bilateral lesions placed more medially in the intermediate tegmentum were far less disruptive (eight out of nine rats ejected milk), though the amount of oxytocin released in this group (8·64±1·88 mu.) was still significantly (P<0·05) lower than controls. All rats with lesions of the central grey (nine) or ventral tegmentum (eight) displayed reflex milk ejection, as did those with multiple lesions of the tectum, central grey and ventral tegmentum (seven); in these three groups the amounts of oxytocin released (13·88±2·68, 13·10±1·90 and 11·04±1·95 mu. respectively) did not differ significantly from controls. Damage to the ventral tegmentum produced an irregular pattern of milk ejection characterized by occasional abnormally short (<2 min) milk-ejection intervals, though the overall number of responses in 3 h was less than that of controls (20·83±1·82 v. 14·50±1·30 mu., P<0·05). In conclusion, these results delineate two mesencephalic areas of particular importance in the milk-ejection reflex: (a) the lateral tegmentum, which appears to be concerned with transmission of the suckling stimulus from the contralateral nipples and is indispensable for oxytocin release, and (b) the ventral tegmentum which, although not an essential component of the reflex, may contribute to the timing of the intermittent milk-ejection responses.


1968 ◽  
Vol 58 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Gorm Wagner ◽  
Anna-Riitta Fuchs

ABSTRACT Previous experiments indicated that in the rabbit, prior administration of ethyl alcohol inhibits the release of oxytocin elicited by suckling. According to preliminary studies, the same applies also in the human. In the present studies, the effect of ethanol on the milk-ejection reflex in post-partum women was investigated more thoroughly. The milk-ejection reflex was induced by suckling of the infant. The uterine response, recorded by external tocography, was used as a measure of the oxytocin release. Alcohol was administered by mouth as whisky or brandy in suitable dilutions in amounts varying from 0.5 to 1.1 g/kg body weight. By comparison of the uterine response to endogenous (released) and exogenous (injected) oxytocin, it was estimated that about 100–250 mU oxytocin are released by the suckling stimulus in the early puerperium. When alcohol was administered before the application of the stimulus, the release of oxytocin was partially or completely inhibited, but the uterus continued to respond to exogenous oxytocin. As shown previously in the rabbit, the effect of alcohol must thus be on the central release mechanism of oxytocin and not on the peripheral response of the target organ to oxytocin. The degree of inhibition of the oxytocin release was dependent on the alcohol concentration in the blood. With an average blood alcohol concentration of 0.07 per cent the uterine response to suckling during one nursing period was less than half of that observed under normal conditions.


1958 ◽  
Vol 149 (936) ◽  
pp. 330-336 ◽  

Following the demonstration by Strieker & Grüter (1928) of the lactogenic effects of anterior-pituitary extracts, the importance of the role of the pituitary in maintaining lactation was further emphasized by observations that removal of the pituitary in the lactating animal resulted in a rapid and complete cessation of lactation (for references, see Folley 1952). For a time it was generally assumed that the loss of the anterior pituitary was the causal factor in the cessation of lactation, but when the role of the posterior pituitary in milk ejection was established it became obvious that interference with the milk-ejection reflex could well be the cause of the failure of lactation after hypophysectomy. It therefore seemed desirable to repeat some of the earlier studies on the effect of hypophysectomy on lactation, in order to determine whether the restoration of milk-ejection by the regular administration of oxytocin would affect the results and possibly allow us to distinguish a failure of milk ejection from a failure of milk secretion. In this connexion it may be noted that reports on the maintenance of lactation after hypophysectomy, by administering anterior-pituitary preparations, have been remarkably few, and this lack of information possibly reflects the unsuccessful outcome of attempts which may have failed because milk ejection was not restored. At Shinfield we have studied the effect of hypophysectomy in the lactating rat, both in the presence and absence of adequate oxytocin therapy, and have confirmed that hypophysectomy results in a rapid and complete inhibition of milk secretion (see Cowie 1957), and there seems to be no reason to doubt that this will also be true for other species.


1953 ◽  
Vol 20 (1) ◽  
pp. 13-15 ◽  
Author(s):  
W. G. Whittlestone

The milk-ejecting activity of the hormones of the posterior-pituitary gland is well known and has been adequately reviewed (1). Most of the published information deals with the lactating dairy cow. In the course of work at this Station involving the lactating sow as a basis for assay of the milk-ejecting hormones (2, 3), data have been collected on the effect of a standard dose of oxytocin. Our normal assay procedure (2) involves giving the animal a preliminary dose of 0·5 unit of oxytocin. Thus over one lactation we have been able to record the time between injection into the ear vein and the onset of milk let-down, and the period during which milk may be obtained by simple hand-milking, for a number of sows. Braude & Mitchell (4) have published figures for the milk let-down effects of doses of oxytocin ranging from 1 to 10 units. The following results were obtained with &5 unit. All sows used were of the Berkshire breed.


1971 ◽  
Vol 50 (1) ◽  
pp. 135-152 ◽  
Author(s):  
J. S. TINDAL ◽  
G. S. KNAGGS

SUMMARY The effect of various types of surgical damage to the forebrain on the release of oxytocin in response to electrical stimulation of the discrete ascending milk-ejection reflex pathway in the mid-brain was investigated in 99 anaesthetized lactating guinea-pigs. Oxytocin release was measured by comparison of experimental milk-ejection responses with the response to i.v. injection of known amounts of synthetic oxytocin. Removal of the entire telencephalon, including cerebral cortex, hippocampi, amygdalae and forebrain rostral to the hypothalamus, did not affect the subsequent release of oxytocin after electrical stimulation of the pathway in the mid-brain, from which it was concluded that the reflex pathway within the forebrain is entirely diencephalic. Transection of the hypothalamus immediately rostral to the paraventricular (PV) nuclei was without effect, while transection immediately caudal to the PV nuclei blocked the release of oxytocin. Destruction of the PV nuclei by a radiofrequency lesion which spared the supraoptic (SO) nuclei blocked the release of oxytocin. Undercutting both PV nuclei so as to isolate them from the ventral hypothalamus blocked the release of oxytocin. Undercutting the PV nucleus ipsilateral to the stimulated side of the mid-brain blocked the release of oxytocin, while undercutting the contralateral PV nucleus had no effect. The PV nuclei, therefore, lie on the ascending path of the milk-ejection reflex, the SO nuclei do not, and, from the mid-brain forwards, the ascending pathway remains uncrossed. The course of the reflex pathway was traced rostrally from the mesodiencephalic junction by making narrow transverse knife-cuts and determining which cuts reduced or blocked the release of oxytocin after mid-brain stimulation. At this level, the pathway on each side of the brain is represented by separate dorsal and ventral paths and in the present study it was found that the ventral path is more important than the dorsal path in terms of oxytocin release. The ventral path passes forward in the medial forebrain bundle, in the far-lateral hypothalamus, while the dorsal path enters the posterior hypothalamus dorsally in the periventricular region at the top of the third ventricle and impinges on the thalamic reuniens nucleus. Shortly afterwards the dorsal path swings abruptly in the lateral direction to join the ventral path in the lateral hypothalamus. The reunited pathway then moves forward in this position until it is level with the PV nuclei, where it swings dorsomedially to relay with the lateral tip of the ipsilateral PV nucleus, and in doing so intermingles with the descending neurosecretory fibres from this nucleus.


2015 ◽  
Vol 226 (2) ◽  
pp. T173-T185 ◽  
Author(s):  
Gareth Leng ◽  
Rafael Pineda ◽  
Nancy Sabatier ◽  
Mike Ludwig

Geoffrey Harris pioneered our understanding of the posterior pituitary, mainly with experiments that involved the electrical stimulation of the supraoptico-hypophysial tract. In the present essay, we explain how his observations included clues to the pulsatile nature of the oxytocin signal – clues that were followed up by subsequent workers, including his students and their students. These studies ultimately led to our present understanding of the milk-ejection reflex and of the role of oxytocin in parturition. Discoveries of wide significance followed, including: the recognition of the importance of pulsatile hormone secretion; the recognition of the importance of stimulus-secretion coupling mechanisms in interpreting the patterned electrical activity of neurons; the physiological importance of peptide release in the brain; the recognition that peptide release comes substantially from dendrites and can be regulated independently of nerve terminal secretion; and the importance of dynamic morphological changes to neuronal function in the hypothalamus. All of these discoveries followed from the drive to understand the milk-ejection reflex. We also reflect on Harris's observations on vasopressin secretion, on the effects of stress, and on oxytocin secretion during sexual activity.


2015 ◽  
Vol 46 (No. 4) ◽  
pp. 108-118 ◽  
Author(s):  
V. Tančin ◽  
R.M. Bruckmaier

The release of oxytocin and milk ejection occurrence in response to teat stimulation are crucial for fast and complete milk removal during milking or suckling. The milk ejection reflex can be disturbed at central or peripheral level under different experimental and practical conditions. The central disturbance results in the lack or insufficient ejection of the alveolar milk into the cistern due to inhibited oxytocin release from pituitary into the blood circulation. The important role in the pathophysiological regulation of the inhibited release of oxytocin is played by an opioid system. Endogenous opioids have suppressive effects on oxytocin release under the normal conditions of milk removal. However under the conditions of disturbed milk ejection their role in dairy cows was not confirmed. Other possible mechanisms involved in the central inhibition of oxytocin release are discussed. In dairy cows as compared with rats the mechanisms involved in the regulation of oxytocin release at the central level remain unclear. The central inhibition of oxytocin release has often been observed in dairy practice during milking of primiparous cows after parturition, suckling by alien calf, calf removal before milking, milking of cows in the presence of own calf, relocation and milking in an unknown milking place. If sufficient released oxytocin cannot induce the transfer of milk from alveoli to cistern, peripheral mechanisms are involved. Peripheral mechanisms are related to the increased levels of catecholamines and/or activation sympathetic nervous system at the udder level. In conclusion, the release of oxytocin and milk ejection efficiency can be very easily suppressed by many factors. The effect of milking conditions on regulation of milk ejection has to be considered. Thus the physiological requirements of dairy cows have to be respected.


1973 ◽  
Vol 57 (3) ◽  
pp. 477-493 ◽  
Author(s):  
J. B. WAKERLEY ◽  
D. W. LINCOLN

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.


1972 ◽  
Vol 52 (2) ◽  
pp. 333-341 ◽  
Author(s):  
G. S. KNAGGS ◽  
A. S. McNEILLY ◽  
J. S. TINDAL

SUMMARY The position of the pathway for the release of oxytocin in the mid-brain was ascertained by exploration of a transverse stereotaxic plane (A4) in 23 anaesthetized goats. Electrical stimulation was applied between a monopolar electrode and an indifferent electrode in the scalp. Oxytocin release was monitored by simultaneous collection of blood samples during stimulation from a catheter in a jugular vein. The blood samples were extracted by the Sephadex G-25 or fuller's earth method and assayed for oxytocin content on the lactating guinea-pig preparation. Oxytocin release occurred occasionally after stimulation of certain sites in the tectum, central grey and reticular formation. Regular releases of oxytocin, however, were only obtained after stimulation of a pathway which was compact and lay in the lateral tegmentum of the mid-brain in association with the spinothalamic tract. The position of this pathway corresponds to that described previously for the afferent pathway of the milk-ejection reflex in the mid-brain of the guinea-pig and rabbit. In these three species therefore, the impulses concerned in oxytocin release appear to ascend through the mid-brain in the spinothalamic tract.


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