Endogenous opioid regulation of stress-induced oxytocin release within the hypothalamic paraventricular nucleus is reversed in late pregnancy: a microdialysis study

Oxytocin secretion into blood in response to swim stress is differentially regulated by endogenous opioids in virgin and pregnant rats. Here, the influence of endogenous opioids on oxytocin release within the hypothalamic paraventricular and supraoptic nuclei was investigated using microdialysis in virgin and pregnant (day 19-21) rats. Rats fitted with a U-shaped microdialysis probe 3 days before testing were injected with naloxone (5 mg/kg body weight, s.c.) or vehicle (sterile saline) and, 3 min later, were forced to swim (10 min at 19 degrees C). Within the paraventricular nucleus, basal and stimulated oxytocin release did not significantly differ between vehicle-treated virgin and pregnant rats. After naloxone, local oxytocin release in response to swimming was lowered in virgin rats (P<0.01), whereas it was further increased in pregnant rats (P<0.01). Within the supraoptic nucleus, basal oxytocin release was significantly lower in pregnant compared to virgin rats (P<0.01). Forced swimming induced a similar rise in intranuclear oxytocin release in both vehicle-treated virgin and pregnant rats, but peak levels were still higher in the virgin controls. In contrast to the paraventricular nucleus, naloxone did not alter swim-induced oxytocin release within the supraoptic nucleus either in virgin or pregnant rats. Vasopressin release in the paraventricular nucleus was also increased by forced swimming but there was no effect of pregnancy or naloxone on it.In summary, in pregnancy, basal and stress-induced oxytocin release within the paraventricular nucleus was not changed, whereas it was blunted within the supraoptic nucleus. Further, within the paraventricular nucleus the excitatory effect of endogenous opioids on local oxytocin release seen in virgins was switched into an inhibitory action in pregnancy. In contrast, endogenous opioids were evidently not involved in the regulation of swim-induced oxytocin release within the supraoptic nucleus either in virgin or pregnant rats. Thus, pregnancy-related neuroendocrine plasticity also includes site-specific functional alterations in opioid receptor-mediated actions in the hypothalamus.     

Effects of naloxone and of intraperitoneal hypertonic saline upon oxytocin release and upon supraoptic neuronal activity

Urethane anaesthetized male rats were given an i.p. injection of hypertonic saline to increase plasma osmotic pressure. This injection resulted in significantly elevated plasma oxytocin levels and increased discharge activity of putative oxytocin cells in the supraoptic nucleus. Subsequent injection of naloxone (1 mg/kg) i.v. resulted in a similarly large increase in plasma oxytocin, but did not affect the discharge activity of putative oxytocin neurones. The results suggest that, following an i.p. injection of hypertonic saline, endogenous opioids act at the neurosecretory terminals to partially inhibit oxytocin release.     

Neurohypophysial opioids and oxytocin secretion: source of inhibitory opioids

Summary When electrical stimuli are applied to the neural stalk of the pituitary, oxytocin, vasopressin, and probably several opioid peptides also contained in nerve terminals in the gland are released: one action of the released opioids appears to be to inhibit oxytocin release by an action that has been likened to pre-synaptic inhibition. Thus, when Clarke et al. (1979) stimulated the neural stalk following intravenous injection of the opioid antagonist naloxone, they observed that the evoked oxytocin release was potentiated. In the present study we confirm this result and show that oxytocin release evoked by stimulation of the supraoptic nucleus is similarly potentiated by naloxone. This finding is consistent with the hypothesis that the opioid responsible for inhibition of oxytocin release coexists with either oxytocin or vasopressin. We further report that the specific -receptor antagonist ICI 174864 does not potentiate oxytocin release either in vivo or in vitro. Thus, it seems unlikely that the enkephalins, putative -receptor agonists present in neurohypophysial fibres, are the opioids responsible for the observed inhibition of oxytocin release.     

Release of oxytocin within the supraoptic nucleus during the milk ejection reflex in rats

Summary To investigate the hypothesis that oxytocin may be released within the magnocellular nuclei in vivo, push-pull cannula perfusions were performed in anaesthetized lactating rats in one supraoptic nucleus of the hypothalamus while recording the intramammary pressure and/or the electrical activity of oxytocin cells in the contralateral supraoptic nucleus. Oxytocin content was measured in samples collected over 15 min, under various conditions: 1) with no stimulation; 2) during suckling and suckling-induced reflex milk ejections; 3) during electrical stimulation of the neurohypophysis by trains of pulses that mimicked oxytocin cell bursts; 4) under osmotic stimulation by i.p. injection of 2 ml of 1.5 M NaCl to evoke a tonic and sustained oxytocin release from the neurohypophysis. Oxytocin release within the supraoptic nucleus increased significantly during the milk ejection reflex and, to a lesser extent, during burst-like electrical stimulation of the neurohypophysis. In suckled rats, the increase started before the first reflex milk ejection occurred. There was no apparent correlation between the amount of oxytocin in the perfusates and the number of milk ejections and oxytocin cell bursts occurring during each perfusion period. The amount of oxytocin in the perfusates further increased during facilitation of the milk ejection reflex by intraventricular injections of oxytocin or its analogue, isotocin. When suckling failed to evoke the milk ejection reflex, there was no change in intra-supraoptic oxytocin release. There was also no change after osmotic stimulation. When the push-pull cannula was positioned outside the supraoptic nucleus, there was no increase in the amount of oxytocin during the three types of stimulation tested. These results provide evidence for an endogenous release of oxytocin within the magnocellular nuclei in lactating rats. It is suggested that the increase in such a release induced by suckling is likely to be a pre-requisite for the onset and the maintenance of the characteristic intermittent bursting electrical activity of oxytocin cells leading to milk ejections.     

Electrophysiological evidence for a projection from the arcuate nucleus to the supraoptic nucleus

The electrical activity of single neurones in the hypothalamic arcuate and supraoptic nuclei was recorded in urethane-anaesthetized rats. Stimulus pulses applied to the supraoptic nucleus antidromically activated 3 out of 41 cells recorded in the ipsilateral arcuate nucleus, confirming that there is a projection from the arcuate nucleus to the region of the supraoptic nucleus. Stimulation of the arcuate nucleus inhibited 17 out of 19 continuously firing (putative oxytocin) supraoptic neurones. Inhibition was followed by a marked post-stimulus excitation in 12 cells. The responses were not abolished by i.v. injection of the opioid antagonist naloxone. Thus at least part of the input to the magnocellular oxytocin system that arises from or passes through the arcuate nucleus, is not mediated by opioid peptides.     

Effects of the selective kappa-opioid agonist U50,488 upon the electrical activity of supraoptic neurones in morphine-tolerant and morphine-naive rats

Spontaneous electrical activity of oxytocin-secreting neurones in the rat supraoptic nucleus is depressed by the mu-opiate receptor agonist morphine, leading to a reduction in plasma oxytocin concentration. In the present experiments, the electrical activity of single neurones was recorded from the supraoptic nucleus of urethane-anaesthetized rats. For 5 days prior to the experiments the rats had received a continuous infusion of either morphine or vehicle into a lateral cerebral ventricle; this regimen of morphine treatment results in tolerance to, and dependence upon, morphine in the central mechanisms controlling oxytocin secretion. Intravenous injection of the specific kappa- opioid agonist U50,488 at low doses resulted in small but significant increases in the electrical discharge activity of some putative oxytocin neurones in both morphine-treated and morphine- naive rats. At higher doses, the kappa-agonist consistently inhibited almost all cells tested. Morphine-treated rats, despite showing tolerance to morphine itself, showed no cross-tolerance to the inhibitory actions of U50,488 upon the oxytocin system. In separate experiments both morphine and U50,488 were effective in inhibiting supraoptic neuronal activation evoked by stimulation of the region anterior and ventral to the third ventricle, and activation following systemic injection of cholecystokinin, suggesting that both opioids act upon the final common pathway — the oxytocin neurone itself.     

The hypothalamic neurosecretory pathways for the release of oxytocin and vasopressin in the cat

1. The neurones of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) were stimulated electrically in lactating cats under chloralose anaesthesia. Milk-ejection responses were used to monitor the release of oxytocin and vasopressin and both hormones were assayed in samples of blood collected during stimulation. The position of the tip of the stimulating electrode was confirmed from brain sections stained selectively for cystine-rich neurosecretory material.2. A previous finding that stimulation of the SON in the cat releases vasopressin without oxytocin was confirmed.3. Stimulation of the PVN caused both hormones to be released. The ratio of their concentrations in blood was variable; this suggests release from separate neurones.4. Both hormones were also released on stimulation of the median eminence but not of the zone lying vertically between this structure and the PVN. No neurosecretory material was detected in this zone. These findings argue against the existence of a direct or medial paraventriculo-hypophysial pathway running downwards along the wall of the third ventricle.5. Study of sections from unstimulated brains confirmed that the tractus paraventricularis cinereus of Greving which runs ventro-laterally from the PVN towards the SON, represents the principal efferent pathway for neurosecretory fibres from the PVN.6. The results are discussed in relation to the problem of the independent release of oxytocin and vasopressin in response to physiological stimulation of the neurohypophysis.     

Opioid binding in a rat neurohypophysial fraction enriched in oxytocin and vasopressin nerve endings

Binding of the opiate antagonists [3H]diprenorphine and [3H]naloxone and of the opioid agonists [3H]Met-enkephalin and [3H]dynorphin(1-8) was studied in a fraction of the rat neurohypophysis containing disconnected oxytocin and vasopressin nerve endings ('neurosecretosomes'). There was specific binding of [3H]diprenorphine in the fraction enriched with neurosecretosomes. This binding was only partially displaceable by naloxone; naloxone binding was stereospecific. Intact and unoxidized [3H]Met-enkephalin was found in the neurosecretosome pellet; binding of the analogue D-Ala-D-Leu-enkephalin was very low. Our data favour the assumption of a direct action of endogenous opioids at the neurosecretory nerve endings.     

Neuroactive steroids attenuate oxytocin stress responses in late pregnancy

In late pregnant rats neuroendocrine stress responses, expressed as increased oxytocin secretion and activation of the hypothalamo-pituitary-adrenal axis, are attenuated. These adaptations preserve the oxytocin store for parturition and prevent pre-term birth, and protect the fetuses from adverse programming by exposure to excess glucocorticoid. Mechanisms of adaptations for oxytocin neurones are reviewed, using challenge with systemic interleukin-1beta, simulating activation of immune signaling by infection, as a stressor of special relevance in pregnancy. In virgin rats, systemic interleukin-1beta stimulates the firing of oxytocin neurones, and hence oxytocin secretion, but interleukin-1beta has no effects in late pregnant rats. This lack of response is reversed by naloxone treatment just before interleukin-1beta administration, indicating endogenous opioid suppression of oxytocin responses in late pregnancy. This opioid presynaptically inhibits noradrenergic terminals impinging on oxytocin neurones. Finasteride pretreatment, inhibiting progesterone conversion to allopregnanolone, a positive GABA(A) receptor allosteric modifier, also restores an oxytocin response to interleukin-1beta. This finasteride effect is reversed by allopregnanolone treatment. In virgin rats allopregnanolone attenuates the oxytocin response to interleukin-1beta, which is exaggerated by naloxone. The effects of naloxone and finasteride in late pregnant rats in restoring an oxytocin response to interleukin-1beta are not additive. Accordingly, allopregnanolone may both enhance GABA inhibition of oxytocin neurone responses to interleukin-1beta, and induce opioid suppression of noradrenaline release onto oxytocin neurones.     

Catecholaminergic mechanisms underlying neurohypophysial hormone responses to unconditioned or conditioned aversive stimuli in rats

Oxytocin release from the neurohypophysis is facilitated by systemic cholecystokinin octapeptide (CCK) administration and noxious stimuli. Oxytocin release after CCK administration is mediated by A2 noradrenergic neurones while the release after noxious stimuli appears to be mediated by A1 noradrenergic neurones. On the other hand, facilitation of vasopressin release after noxious stimuli is not dependent upon noradrenergic neurones but on dopamine receptors. Environmental stimuli previously paired with noxious stimuli (conditioned fear stimuli) or novel environmental stimuli facilitate oxytocin release and suppress vasopressin release. These neuroendocrine responses to conditioned fear stimuli, but not to novel stimuli, are impaired by central noradrenaline depletion or i.c.v. adrenoceptor antagonists. These data suggest that there are at least two types of stress responses in neuroendocrine systems, one noradrenaline dependent, and one noradrenaline independent. It is also suggested that noradrenergic neurones are functionally heterogeneous in the control of oxytocin release.     

Electrical activity in the supraoptic and paraventricular nuclei associated with neurohypophysial hormone release

1. Unit recordings were made from the hypothalamus in anaesthetized male rats using steel or glass micro-electrodes.2. Stimuli which are known to release vasopressin and oxytocin (electrical stimulation of the central end of the severed right vagus nerve and intracarotid injection of CaCl(2) solution) also excite units in the supraoptic and paraventricular nuclei. In addition, these units are excited by intracarotid injections of carbachol, acetylcholine and NaCl (5%) which are less effective stimuli for vasopressin release.3. These stimuli also excite units from which potentials can be evoked by stimulation of the pituitary stalk and which are likely to be neurosecretory neurones. Neurosecretory neurones can conduct electrical impulses like other less specialized nerve cells. Estimations of conduction velocity range between 0.4 and 1.3 m/sec.4. The proportion of units in the supraoptic and paraventricular nuclei which are excited and the degree of excitation corresponds approximately to the amount of vasopressin released by the stimuli. In addition, excitation of the supraoptic nucleus seems to be more directly associated with vasopressin release and excitation of the paraventricular nucleus with oxytocin release.     

The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the rat

Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo-neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo-neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA ( N -methyl-D-aspartate) and non-NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo.     

Characterization of the responses of oxytocin- and vasopressin-secreting neurones in the supraoptic nucleus to osmotic stimulation

1. Extracellular action potentials were recorded from forty antidromically identified single units in the supraoptic nucleus of lactating, urethane-anaesthetized female rats. The activity was monitored both during reflex milk ejection and during an increase of 10-15 m-osmole/kg in plasma osmotic pressure induced by intraperitoneal injection of 1 ml. of 1.5 M-NaCl solution.2. About half (eighteen) the cells showed a burst of activity before reflex milk ejection and were dubbed oxytocin cells. Oxytocin cells responded to a hypertonic injection with a smooth sustained threefold increase in firing rate.3. The remainder (twenty-two) showed no burst of activity before reflex milk ejection and were dubbed vasopressin cells. Vasopressin cells doubled their firing rate as plasma osmotic pressure increased. Neither cell type increased its firing rate after injections of isotonic NaCl.4. A phasic firing pattern was rarely seen in slow firing vasopressin cells (< 2 spikes/sec) but was seen in almost all vasopressin cells (twelve out of fourteen) firing between 3 and 8 spikes/sec. Above 8 spikes/sec, some vasopressin cells fired continuously. Phasic firing was only once encountered in an oxytocin cell.5. The firing rate of both oxytocin and vasopressin cells decreased when plasma osmotic pressure was reduced 10-15 m-osmole/kg by an intragastric water load of 10 ml.6. Hypothalamic cells lying just outside the supraoptic nucleus did not show a consistent response to injection of hypertonic NaCl.7. Clearly, both oxytocin and vasopressin cells are osmoresponsive, but phasic firing is characteristic of stimulated vasopressin cells. Thus, osmotic activation allows discrimination between oxytocin- and vasopressin-secreting neurones.     

Axon collaterals of supraoptic neurones: Anatomical and electrophysiological evidence for their existence in the lateral hypothalamus

The magnocellular neurones of the supraoptic nucleus which synthesize and secrete vasopressin and oxytocin have been commonly regarded as simple “output” neurones in that they receive an input, generate an action potential and in turn release hormone from their terminals in the posterior pituitary. Three lines of evidence are presented which suggest that rat supraoptic nucleus neurones also have axon collaterals which terminate in the hypothalamus close to the nucleus. Small injections of horseradish peroxidase were made directly into the nucleus in hypothalamic slices, allowing visualization of the axons of supraoptic neurones. Collaterals of these axons could be observed in regions both dorsal and dorsolateral to the supraoptic nucleus. In a separate series of experiments, sections of perfusion-fixed hypothalamus were stained for vasopressin and oxytocin using specific antisera. Peptide-containing collaterals of both types were observed near the supraoptic nucleus, in a region similar to that seen after horseradish peroxidase injections. Finally, electrophysiological studies were carried out on hypothalamic slices containing the supraoptic nucleus. A small concentric bipolar stimulating electrode was placed directly into the nucleus and activity of lateral hypothalamic neurones within 0.1–1 mm of the nucleus was recorded. Of 68 neurones studied, 52 were exicted by supraoptic stimulation via a synaptic pathway that could be blocked by Ca²⁺ -free solutions containing 18mM Mg²⁺.These studies suggest that supraoptic neurones communicate via axon collaterals with other neurones in the lateral hypothalamus, in addition to their previously well characterised functional role in neurosecretion.     

Vasopressin and oxytocin in the rat spinal cord: distribution and origins in comparison to [Met]enkephalin, dynorphin and related opioids and their irresponsiveness to stimuli modulating neurohypophyseal secretion

Immunoreactive-vasopressin, -oxytocin, -dynorphin, -dynorphin-(1-8), -alpha-neo-endorphin and -[Met]enkephalin were, in each case, present in greater concentrations in dorsal as compared to ventral, and lumbo-sacral as compared to cervico-thoracic, spinal cord. These differences were significantly more pronounced for vasopressin and oxytocin than for the other peptides. Lesions of the hypothalamic paraventricular nucleus depleted levels of immunoreactive-vasopressin and -oxytocin throughout the cord whereas levels of the opioid peptides therein were unaffected. In contrast, destruction of either the supraoptic or suprachiasmatic nucleus failed to change the content of immunoreactive-vasopressin, -oxytocin or any of the opioid peptides in the cord. Dehydration for 3 days depressed levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate lobe of the pituitary. In distinction, the levels of these were not modified in the spinal cord. Further, treatment with the synthetic corticosteroid, dexamethasone, elevated levels of immunoreactive-vasopressin, -oxytocin and -dynorphin in the neurointermediate pituitary whereas these were unaffected in the spinal cord. It is concluded that vasopressin and oxytocin in the spinal cord are predominantly derived from the paraventricular nucleus, localized in dorsal lumbo-sacral regions of the cord and insensitive to endocrinological manipulations. These pools may, thus, be modulated differently from their counterparts in the neurohypophysis and have a differing role, possibly in the control of the primary processing, autonomic or motor junctions. Further, there is no evidence from these or our prior studies for a close interrelationship of spinal cord vasopressin with dynorphin-related peptides (or oxytocin with [Met]enkephalin), likewise in contrast to the neurohypophysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioural impact of intraseptally released vasopressin and oxytocin in rats

The two nonapeptides arginine vasopressin and oxytocin are not only secreted from the neurohypophysis into the general circulation but are also released intracerebrally. Our recent research has focused on the release patterns and effects of oxytocin and vasopressin in brain areas, such as the septum and hypothalamus, that are thought to be involved in the regulation of (1) behavioural responses and (2) responses of the hypothalamo-neurohypophysial system (HNS) to stressor exposure in rats. The results demonstrate that combined physical and emotional stress (induced by exposure to forced swimming) selectively triggers the release of vasopressin within all brain areas under study but not into the general circulation. Under emotional stress conditions (induced by exposure to the 'social defeat'procedure), however, oxytocin rather than vasopressin release increased within the hypothalamus and septum. Experiments aimed at revealing the neuroendocrine and behavioural relevance of the local nonapeptide release provided evidence for an involvement of vasopressin in the regulation of HNS activity (within the hypothalamus) and, moreover, in acute stress-coping strategies, anxiety-related behaviour and learning and memory processes (within the septum). The observed dissociation between central and peripheral nonapeptide release not only supports the hypothesis that plasma vasopressin and oxytocin concentrations do not necessarily reflect central release patterns but also suggests vasopressin and oxytocin neurones are able to independently release their nonapeptide from different parts of their neuronal surface (e.g. from somata/dendrites vs. axon terminals). This remarkable regulatory capacity provides the basis for an differential involvement of vasopressin, and probably also oxytocin, in the co-ordination of neuroendocrine activity, emotionality and cognition at different brain levels to ensure an appropriate behavioural response of the organism to stressful stimuli     

Facilitative role of prolactin-releasing peptide neurons in oxytocin cell activation after conditioned-fear stimuli

Emotional stress activates oxytocin neurons in the hypothalamic supraoptic and paraventricular nuclei and stimulates oxytocin release from the posterior pituitary. Oxytocin neurons in the hypothalamus have synaptic contact with prolactin-releasing peptide (PrRP) neurons. Intracerebroventricular administration of PrRP stimulates oxytocin release from the pituitary. These observations raise the possibility that PrRP neurons play a role in oxytocin response to emotional stress. To test this hypothesis, we first examined expression of Fos protein, an immediate early gene product, in the PrRP neurons in the medulla oblongata after conditioned-fear stimuli. Conditioned-fear stimuli increased the number of PrRP cells expressing Fos protein especially in the dorsomedial medulla. In order to determine whether PrRP cells projecting to the supraoptic nucleus are activated after conditioned-fear stimuli, we injected retrograde tracers into the supraoptic nucleus. Conditioned-fear stimuli induced expression of Fos protein in retrogradely labeled PrRP cells in the dorsomedial medulla. Finally we investigated whether immunoneutralization of endogenous PrRP impairs oxytocin release after emotional stimuli. An i.c.v. injection of a mouse monoclonal anti-PrRP antibody impaired release of oxytocin but not of adrenocorticotrophic hormone or prolactin and did not significantly change freezing behavior in response to conditioned-fear stimuli. From these data, we conclude that PrRP neurons in the dorsomedial medulla that project to the hypothalamus play a facilitative role in oxytocin release after emotional stimuli in rats.     

Possible morphological bases for synchronisation of neuronal firing in the rat supraoptic nucleus during lactation

Oxytocin-containing neurones in the supraoptic and paraventricular nuclei of lactating rats display a periodic activation which results in a pulsatile release of hormone before each reflex milk ejection induced by suckling. This electrical activity occurs in an all-or-none fashion and is synchronised in the whole population of oxytocin neurones in both nuclei. The present report describes changes in the ultrastructure of the supraoptic nucleus of lactating animals which may serve as morphological bases for such a functional synchronisation.In the supraoptic nuclei of normal rats, neurosecretory neurones are usually separated by elements of the neuropil, particularly glial processes. At rare intervals, adjacent neurosecretory somata, and dendrites, are seen to be in direct apposition. The only specialisations apparent between the contiguous membranes are occasional attachment plates. In nuclei of lactating rats, quantitative analysis indicated that 34% of profiles of the sectioned neurosecretory cell bodies were in direct contact with each other and 22% with profiles of dendrites, a 5-fold increase over the corresponding frequencies observed in normal male and virgin female animals. Such contacts involved 10% of the total measured soma surface membrane (compared to 1.5% in the controls). The number of attachment plates supporting the apposing membranes also increased significantly as did the mean size of the individual appositions. There was also a higher incidence of presynaptic terminals contacting more than one post-synaptic element (soma or dendrite) in the same plane of section, a rare phenomenon in the normal nucleus. No further increases were evident in these appositional relations in virgin female and lactating rats deprived of water for one day, a stimulus which enhances vasopressin release.It is postulated that the structural reorganisation observed in the nuclei of lactating animals may lead to electrical interactions between the neurosecretory cells and may thus be one of the factors supporting the synchronisation of neuronal activity during the episodic release of oxytocin.     

Lack of response in the release of oxytocin and vasopressin from isolated neurohypophyses to dopamine,met-enkephalin and leu-enkephalin

Summary We investigated the effects of dopamine, met-enkephalin and leu-enkephalin on basal and ouabain-stimulated release of oxytocin and vasopressin from isolated neurointermediate lobes. The present study revealed that neurohypophyseal hormone release was not affected by dopamine, neither from lobes of untreated rats nor from those of rats with dopamine-deficiency (pretreated with -methyl-p-tyrosine-methylester). Likewise, metoclopramide, a dopamine antagonist, was unable to alter the neurohypophyseal hormone release. Our results also indicate that the opioid peptides met-enkephalin and leu-enkephalin do not influence spontaneous or ouabain-stimulated oxytocin and vasopressin release, which is in accordance with our findings that naloxone under our experimental conditions is also ineffective.