Role of Non-NMDA Receptors in Osmotic and Glutamate Stimulation of Vasopressin Release: Effect of Rapid Receptor Desensitization

Previous studies demonstrated that the increase in vasopressin (VP) release and induction of VPmRNA content by osmotic stimulation was blocked by kynurenic acid, a non-specific antagonist of excitatory amino acid (EAA) receptors. In order to identify the type of EAA receptor involved, perifused explants of the hypothalamo-neurohypophyseal system (HNS) were exposed to a ramp increase in osmolality (40 mOsm over 6  h achieved by increasing NaCl) in the presence and absence of 10  μ m 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of non- n -methyl-d-aspartate (NMDA) excitatory amino acid receptors. Vasopressin release and VP mRNA content were significantly increased by exposure to the osmotic stimulus. 6,7-dinitroquinoxaline-2,3-dione inhibited osmotically stimulated VP release ( F =16.65, P=0.0008) without significantly reducing basal release. It also prevented the osmotically stimulated increase in VP mRNA content (P<0.05). Although these results implicated glutamate, the primary endogenous ligand for EAA receptors, in the regulation of VP, exogenous glutamate was ineffective in stimulating VP release from HNS explants in either low-Mg²⁺ or Mg²⁺-replete medium. However, blockade of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor desensitization with cyclothiazide (100  μ m ) caused a marked increase in VP release in response to 100  μ m glutamate, and blockade of kainate receptor desensitization with concanavalin A resulted in a small, but significant increase in VP release in response to 1  m m glutamate. These results support a role for non-NMDA receptor activation in osmotic regulation of VP release.     

Quantitative Comparisons Between the Electrical Activity of Supraoptic Neurons and Vasopressin Release in vitro

The firing rate of antidromically identified neurons in the tuberal portion of the rat supraoptic nucleus and vasopressin release were compared in an in vitro preparation of the hypothalamo-neurohypophysical system. Extracellular potentials were isolated and held while the perifusing medium was collected for radioimmunoassay of vasopressin. Neurons in the tuberal portion of the supraoptic nucleus were induced to first bursts of action potentials by injecting supra-threshold concentrations (0.01, 0.1 and 1 mM) of the α₁-agonist phenylephrine into the perifusing line. Phenylephrine caused a dose-dependent release of vasopressin into the perifusate and a dose-dependent increase in the peak firing rate, initial burst duration and the total number of action potentials (compared to a 10 min control period) of the recorded neurons. Peak firing rate and peak vasopressin release both increased linearly with the log of the phenylephrine dose, but the efficiency ratio of the increase in vasopressin release to the increase in firing rate was greater from the middle to the highest dose than it was for the lowest to the middle dose, indicating a possible facilitation of hormone release with higher firing frequencies. The total amount of vasopressin released in 10 min post-injection and the total number of evoked action potentials in the same period also increased linearly, but in this case there was no change in the efficiency ratio between the low to middle and the middle to high doses of phenylephrine. Release of vasopressin to phenylephrine was dependent on an intact neural stalk, and in a separate group of isolated neural lobes, 1 mM phenylephrine did not significantly alter the peak or total amount of vasopressin released to an electrical stimulus given in the pattern of an evoked burst. In another group of explants the temporal relationship between firing rate and vasopressin release was examined after a single dose of 1 mM phenylephrine. In these explants the true time-course of release was estimated using a deconvolution procedure which corrected for diffusion of the hormone. Mean vasopressin release and spike activity were still elevated above baseline 4 to 5 min after the first elicited burst, suggesting that the latter parts of the initial burst and/or the after-discharges contribute to the prolonged vasopressin release. However, there was a dramatic drop in the efficiency ratio (vasopressin release/peak firing rate) from the first to the second minute following stimulation. Thus, changes in the frequency of action potentials generated by supraoptic neurons can be directly related to simultaneous changes in the rate of vasopressin release in the same preparation. The results suggest that elevations in firing rate are accompanied by an increased rate of vasopressin release, but as has been demonstrated in isolated neural lobes, this relationship is probably not constant across different stimulation strengths or within a single burst.     

Dendritic Release of Vasopressin and Oxytocin

In addition to the release of neurotransmitters from their axon terminals, several neuronal populations are able to release their products from their dendrites. The cell bodies and dendrites of vasopressin- and oxytocin-producing neurones are mainly located within the hypothalamic supraoptic and paraventricular nuclei and neuropeptide release within the magnocellular nuclei has been shown in vitro and in vivo . Local release is induced by a range of physiological and pharmacological stimuli, and is regulated by a number of brain areas; locally released peptides are mainly involved in pre- and postsynaptic modulation of the electrical activity of magnocellular neurones. Spatial and temporal differences between peptide release within the nuclei and that from the distant axonal varicosities indicate that the release mechanisms are at least partially independent, supporting the hypothesis of locally regulated dendritic release of vasopressin and oxytocin. In this respect, magnocellular neurones show similarities to other neuronal populations and thus autoregulation of neuronal activity by dendritic neuromodulator release may be a general phenomenon within the brain.     

Non-Phasic Discharge and Osmoresponsiveness of Cat Magnocellular Neuroendocrine Cells

Repetitive bursting (phasic firing) generated endogenously by magnocellular neuroendocrine cells (MNCs) in the rat facilitates systemic release of vasopressin from axon terminals in the neurophypophysis. However, little is known of how MNCs function in other mammals. Using coronal slices of hypothalamus we studied the firing behaviour and intrinsic membrane properties of homologous neurons in the cat supraoptic nucleus where vasopressinergic MNCs outnumber oxytocinergic cells. Less than 1% of units recorded in cat supraoptic nuclei (2 of 270) spontaneously fired in a phasic mode compared to 39% in the rat (90 of 230). A discrete level of steady current across the extracellular recording micropipette promoted phasic firing in 66 of 152 non-phasic units tested in rat supraoptic nuclei, but no phasic activity in 189 units from the cat. One or several stimuli applied dorsal to supraoptic nuclei triggered a single burst (afterdischarge) in 115 of 180 MNC units from the rat, whereas none of 173 MNC units tested in the cat fired an afterdischarge. Intracellular recordings from 56 feline MNCs revealed that unlike the rat, spike depolarizing afterpotentials were absent in all cells. This explains both the absence of phasic firing and the inability to trigger regenerative bursts in the intact cat. The possible Osmoresponsiveness of cat MNCs was examined using unit recording. These units reversibly increased their firing rate as osmolality was elevated with mannitol or NaCl (10 to 100 mOsm/kg), comparable to rat units. However, in no case did hyperosmotic conditions elicit phasic firing. We conclude that cat MNCs lack a regenerative burst capability but that unit Osmoresponsiveness is comparable to rat MNC units. We hypothesize that since the kidney of the cat normally functions at high efficiency in terms of water resorption, there may be little need for the rapid and pronounced elevation in vasopressin release evoked by phasic firing.     

Emotional Stress Triggers Intrahypothalamic But Not Peripheral Release of Oxytocin in Male Rats

Previous experiments have shown that an exposure to defined stressors activates not only the 'classical' endocrine stress response but also the intrahypothalamic and peripheral release of oxytocin. In the present study we investigated the effects of an acute social defeat experience on the release of oxytocin within the hypothalamic supraoptic nucleus, just outside of the supraoptic nucleus toward the midline within the anterior ventro-lateral part of the hypothalamus, and into plasma of adult male rats. Our results demonstrate that emotional stress triggers the release of oxytocin into the extracellular fluid of both the supraoptic nucleus and the anterior ventro-lateral part of the hypothalamus (up to approximately 320% and 170%, respectively). Interestingly, oxytocin release within the latter brain area, which is likely to originate from axons forming the hypothalamo-neurohypophysial tract, was higher in absolute terms than that within the supraoptic nucleus itself, both under basal conditions and in response to social defeat. In contrast to intrahypothalamic release patterns, plasma oxytocin levels remained virtually unchanged upon stressor exposure. This demonstrates that the release of oxytocin within the hypothalamus is triggered by emotional stress. Furthermore, it indicates that under physiological conditions the release of oxytocin from the dendrites and somata upon axon terminals in the neurohypophysis is differentially regulated. Although not yet studied in detail, it may be hypothesized that the spatial and temporal release pattern of oxytocin is controlled by integrative neuronal networks at different brain levels (including hypothalamus and posterior pituitary) to ensure the appropriate involvement of this peptide in the stress response of the animal.     

A deficit of brain dystrophin 71 impairs hypothalamic osmostat

Patients with Duchenne muscular dystrophy (DMD) and mdx mice, devoid of dystrophin proteins, show altered ionic homeostasis. To clarify dystrophin's involvement in the central control of osmotic stimuli, we investigated the effect of the disruption of Dp71, the major form of dystrophin in the brain, on the hypothalamoneurohypophysis system (HNHS) osmoregulatory response. Dp71 and Dp140 are the principal DMD gene products in the supraoptic nucleus (SON) and neurohypophysis (NH). They are present in astrocyte and pituicyte end‐feet, suggesting involvement in both intrinsic osmosensitivity of the SON and vasopressin (AVP) release from the NH. In Dp71‐null mice, the cellular distribution of Dp140 was modified, this protein being detected on the membrane of magnocellular soma. The plasma osmolality of Dp71‐null mice was lower than that of wild‐type mice under normal conditions, and this difference was maintained after salt loading, indicating a change in the set point for osmoregulation in the absence of Dp71. The increase in AVP levels detected in the SON and NH of the wild‐type was not observed in Dp71‐null mice following salt loading, and the increase in AVP mRNA levels in the SON was smaller in Dp71‐null than in wild‐type mice. This suggests that Dp71 may be involved in the functional activity of the HNHS. Its astrocyte end‐feet localization emphasizes the importance of neuronal–vascular–glial interactions for the central detection of osmolality. In the SON, Dp71 may be involved in osmosensitivity and definition of the “osmostat,” whereas, in the neurohypopohysis, it may be involved in fine‐tuning AVP release. © 2009 Wiley‐Liss, Inc.     

Computer-Aided Mapping of Vasopressin Neurons in the Hypothalamus of the Male Golden Hamster: Evidence of Magnocellular Neurons that do not Project to the Neurohypophysis

Vasopressin-sensitive neurons in the region of the anterior hypothalamus are necessary for the mediation of flank marking behavior in the Golden hamster. The precise nature of the vasopressinergic innervation to the anterior hypothalamus is unknown. In this study we seek to examine the potential sources of this innervation by mapping and counting the vasopressin-immunoreactive neurons that contribute to the hypothalamo-neurohypophysial system, and those that do not. Vasopressin-immunoreactive neurons in the hypothalamus were visualized by immunocytochemistry. Sections were mapped with a computer-aided microscope system, and labeled neurons counted. Two-dimensional maps were stacked into a three-dimensional wireframe model which could be manipulated for further examination. The average number of vasopressin neurons was 3,135, with over 60% of all perikarya localized to the lateral supraoptic nucleus. In a double-labeling study, neurons contributing to the hypothalamo-neurohypophysial system were retrogradely labeled by the injection of horseradish peroxidase into the neurohypophysis. The enzyme reaction product was visualized by treatment with tetramethylbenzidine followed by nickel-conjugated diaminobenzidine. Sections were subsequently stained for vasopressin by immunocytochemistry. Single- and double-stained neurons from serial sections were mapped and counted. Wireframe and contoured three-dimensional representations were generated. The average number of neurons projecting to the neurohypophysis was 5,619. However, an average of 981 neurons was immunoreactive to vasopressin but devoid of horseradish peroxidase. The greatest number of these non-projecting perikarya were found in and around the anterior hypothalamus, localized primarily in the lateral and medial aspect of the supraoptic nuclei, the ventral area of the paraventricular nucleus, and the nucleus circularis. By comparing the number of non-projecting neurons found by double-staining to the total cell count of the entire vasopressin system, it was estimated that approximately 30% of all vasopressin neurons in and around the anterior hypothalamus did not project to the neurohypophysis. Based on the distribution and localization of the non-projecting perikarya, it is speculated that these neurons may provide neurotransmitter for vasopressin-dependent flank marking in the male Golden hamster.     

Inward Rectification (Ih) in Immunocytochemically-ldentified Vasopressin and Oxytocin Neurons of Guinea-Pig Supraoptic Nucleus

Intracellular recordings of magnocellular neurons from the supraoptic nucleus of guinea-pigs were made with KCI/K citrate- and biocytin-filled electrodes. Fifty of 99 cells exhibited a time-dependent inward rectification (TDR). The TDR was activated during hyperpolarizing current pulses to membrane potentials more hyperpolarized than −75 mV. In voltage-clamp recordings, an inward current appeared at voltage steps more hyperpolarized than −75 mV, with properties similar to the slow inward rectifier (I_h) described in other tissues. The I_h was blocked by 2 mM CsCI. BaCI₂ (100 to 500 μM) did not block the I_h. Immunocytochemical identification of the recorded cells revealed that both vasopressin (AVP)- and oxytocin (OT)- containing neurons exhibited an I_h.     

Reduced Oxytocin Release from the Neural Lobe of Lactating Rats is Associated with Reduced Pituitary Content and does not Reflect Reduced Excitability of Oxytocin Neurons

Lactating rats show reduced oxytocin release compared with virgin female rats in response to a variety of stimuli, including stress and osmotic stimulation. We sought to establish whether this is a consequence of a reduced response in the oxytocin cells, or of a change in stimulus-secretion coupling at the level of the neurosecretory terminals in the neural lobe. Blood sampling experiments in anaesthetized rats showed that systemic administration of cholecystokinin resulted in significantly less oxytocin release in lactating rats than in virgin female rats. Electrophysiological recordings of single cells in the supraoptic nucleus, however, showed no difference in the responsiveness of oxytocin cells to this stimulus. Oxytocin release evoked by electrical stimulation or by depolarization with high potassium solutions was lower in isolated neural lobes from lactating rats than in glands from non-lactating rats, whereas evoked vasopressin release was similar in the two groups. The lactating rat neural lobes had a reduced oxytocin content: to study the consequences of depletion we compared hormone release evoked by electrical stimulation in vitro in neural lobes from normal male rats, and from male rats given 2% NaCI to drink for 2 or 4 days. Saline drinking resulted in a reduction in gland content of both oxytocin and vasopressin, and the evoked release of both hormones was also significantly reduced when expressed as a percentage of the gland content, as was also seen for oxytocin release for glands from lactating rats. Finally, measurement of the extracellular potassium response to stimulation of the isolated neural lobe as an index of the excitability of neural lobe neurosecretory axons was unchanged in lactating rats compared with virgin female rats. Together, the data indicate that reduced oxytocin release observed in lactating rats is a simple consequence of reduced oxytocin content in the neural lobe rather than of a reduced excitability of the oxytocin neurons.     

Effects of lesions in the hypothalamic paraventricular, supraoptic and suprachiasmatic nuclei on vasopressin and oxytocin in rat brain and spinal cord

The content of arginine vasopressin and oxytocin in various extrahypothalamic sites of the rat brain and spinal cord was determined by specific radioimmunoassays after lesions had been made in either the paraventricular (PVN), supraoptic (SON) or suprachiasmatic nuclei (SCN). In some animals all 3 nuclei were destroyed together. The PVN provided a considerable amount of the vasopressin innervation of the solitary tract nucleus, and most of that in the spinal cord. Oxytocin was removed from some areas after lesions of the PVN and, again, most of this peptide was lost from the spinal cord. Lesions of the SCN did not appear to be followed by significant quantitative changes in either hormone in any of the areas studied. Lesions of the SON resulted in loss of oxytocin, particularly in the periventricular grey and some other areas, suggesting that extrahypothalamic projections from this nucleus may be more important than was previously assumed. Lesions of all 3 nuclei which included destruction of accessory hypothalamic nuclei resulted in a much more widespread loss of vasopressin and oxytocin, but there was preservation of both peptides in the dorsal raphe nucleus and much of those present in the locus coeruleus. It is concluded that the contribution of the classical hypothalamic nuclei to the extrahypothalamic content of vasopressin and oxytocin in rat brain is less than was originally believed, and that there are areas of the brain such as the locus coeruleus and dorsal raphe nucleus in which the source of these peptides may be outside the hypothalamus.     

Diverse roles of G-protein coupled receptors in the regulation of neurohypophyseal hormone secretion

The magnocellular neurones in the supraoptic nucleus project to the neural lobe and release vasopressin and oxytocin into the peripheral circulation, where they act on the kidney to promote fluid retention or stimulate smooth muscles in the vasculature, uterus and mammary glands to support blood pressure, promote parturition or induce milk let-down, respectively. Hormone release is regulated by complex afferent pathways carrying information about plasma osmolality, blood pressure and volume, cervical stretch, and suckling. These afferent pathways utilise a broad array of neurotransmitters and peptides that activate both ligand-gated ion channels and G-protein coupled receptors (GPCRs). The ligand-gated ion channels induce rapid changes in membrane potential resulting in the generation of action potentials, initiation of exocytosis and the release of hormone into the periphery. By contrast, the GPCRs activate a host of diverse signalling cascades that modulate action potential firing and regulate other cellular functions required to support hormone release (e.g. hormone synthesis, processing, packaging and trafficking). The diversity of these actions is critical for integration of the distinct regulatory signals into a response appropriate for maintaining homeostasis. This review describes several diverse roles of GPCRs in magnocellular neurones, focusing primarily on adrenergic, purinergic and peptidergic (neurokinin and angiotensin) receptors.     

Interleukin-1β Stimulates both Central and Peripheral Release of Vasopressin and Oxytocin in the Rat

Simultaneous microdialysis in the brain and blood was used to monitor the release of vasopressin and oxytocin within the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei and into the systemic circulation of urethane-anaesthetized male rats before and after central administration of interleukin-1β (IL-1β). Following intracerebroventricular infusion of the cytokine (200 ng/5 μl), the content of vasopressin (up to 278% compared to vehicle-treated control, P < 0.01 compared to vehicle-treated control and preinfusion baseline) but not oxytocin (up to 148%, not significant) in 30-min blood microdialysates was found to be increased. This peripheral release was accompanied by a transient rise in vasopressin (up to 163%, P < 0.05) and oxytocin (up to 182%, P < 0.05) release within the SON, the peak typically occurring during the first and second 30-min collection intervals after IL-1 β respectively. In contrast, in the simultaneously microdialysed PVN, both vasopressin and oxytocin failed to respond to intracerebroventricular IL-1 β. In another series of experiments, IL-1 β was directly infused (20 ng0.5 μl) into either the SON or PVN during microdialysis of the corresponding nucleus. The cytokine caused a significant and immediate rise in intra-SON release of both vasopressin (up to 225%, P < 0.01) and oxytocin (up to 178%, P < 0.05). Again, in the PVN, nonapeptide release, although tending to be stimulated in response to intranuclear IL-1 β, failed to reach statistical significance. The cytokine-induced central and peripheral release pattern appeared to be independent of the rise in body temperature observed after IL-1 β administration. In a third series of experiments, bilateral administration of IL-1 β into the SON (20 ng/0.5 μl) failed to alter peripheral release of both vasopressin and oxytocin into the systemic circulation. The increase in central nonapeptide release in response to IL-1 β shown in this paper supports the hypothesis that at least vasopressin might act to oppose central effects of the cytokine, including those on thermoregulation and behaviour, in this way contributing to the neuroendocrine-immune dialogue at brain level.     

Osmotic Modulation in Glutamatergic Excitatory Synaptic Inputs to Neurons in the Supraoptic Nucleus of Rat Hypothalamus in vitro

To clarify influence of osmotic stimulation on the excitatory synaptic inputs to the neurosecretory cells of the supraoptic nucleus (SON), the blind patch technique was used in rat hypothalamic slice preparations. Stable whole-cell recordings were made from 22 neurons in the SON. To observe spontaneous excitatory postsynaptic currents (sEPSCs) in the SON neurons, membrane potentials were clamped between −50 and −90  mV. The effects of hypertonic stimulation on the frequency of the sEPSCs were tested in 18 SON neurons. Bath application of mannitol 30 or 60  mM increased the frequency of the sEPSCs. During the application of mannitol (60  mM), the frequency of the sEPSCs increased in 12 of 15 neurons without a change in amplitude. Hypertonic stimulation with NaCl (30  mM) had similar effects to that of mannitol. The increased frequency of miniature EPSCs (mEPSCs) during mannitol application persisted in the presence of TTX in all 8 SON neurons tested with no change in amplitude. Both the non-NMDA antagonist CNQX at 10–30  μM (n=6) and the non-selective glutamate antagonist kynurenic acid at 1  mM (n=3) almost completely blocked the EPSCs while the NMDA antagonist AP-5 at 10  μM had no effect on the frequency of the EPSCs in the 4 neurons tested. During application of CNQX, mannitol (60  mM) was added to the perfusion medium in 3 SON neurons. Under these conditions, mannitol had no effect on the frequency of EPSCs. We conclude that hypertonic stimulation directly influences glutamatergic inputs to the neurosecretory cells of the SON by an action on the presynaptic terminals and enhances the excitatory synaptic events.     

Electrophysiological Identification of the Functional Presynaptic Nerve Terminals on an Isolated Single Vasopressin Neurone of the Rat Supraoptic Nucleus

Release of arginine vasopressin (AVP) and oxytocin from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is under the control of glutamate‐dependent excitation and GABA‐dependent inhibition. The possible role of the synaptic terminals attached to SON neurones has been investigated using whole‐cell patch‐clamp recording in in vitro rat brain slice preparations. Recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of MNCs at the synaptic level in the SON. In the present study, excitatory glutamatergic and inhibitory GABAergic synaptic inputs were recorded from an isolated single SON neurone cultured for 12 h, using the whole‐cell patch clamp technique. Neurones expressed an AVP‐enhanced green fluorescent protein (eGFP) fusion gene in MNCs. In addition, native synaptic terminals attached to a dissociated AVP‐eGFP neurone were visualised with synaptic vesicle markers. These results suggest that the function of presynaptic nerve terminals may be evaluated directly in a single AVP‐eGFP neurone. These preparations would be helpful in future studies aiming to electrophysiologically distinguish between the functions of synaptic terminals and glial modifications in the SON neurones.     

The Effect on Vasopressin Release of Microinjection of Cholinergic Agonists into the Paraventricular Nucleus of Conscious Rats

We have studied in conscious unrestrained rats under basal conditions the effect of activation of muscarinic and nicotinic receptors in the paraventricular nucleus on vasopressin secretion and mean arterial blood pressure. The microinjection of oxotremorine (0.2, 2 or 20 ng), a specific muscarinic agonist, produced a substantial, dose-dependent, transient increase in the plasma vasopressin concentration. There was also a rise in mean arterial blood pressure and a bradycardia that followed the same time-course as the change in plasma vasopressin levels. The microinjection of nicotine (0.1, 1 or 10 HQ) into the paraventricular nucleus had only questionable effects on vasopressin release and mean arterial blood pressure; heart rate was unaffected. These findings suggest that muscarinic receptors may be of primary importance in the paraventricular nucleus in the Cholinergic stimulation of vasopressin release.     

Central Endogenous Vasopressin Induced by Central Salt-Loading Participates in Body Fluid Homeostasis through Modulatory Effects on Neurones of the Paraventricular Nucleus in Conscious Rats

Peripherally secreted arginine vasopressin (AVP) plays a role in controlling body fluid homeostasis, and central endogenous AVP acts as a neurotransmitter or neuromodulator. The limbic system, which appears to exert an inhibitory effect on the endocrine hypothalamus, is also innervated by fibres that contain AVP. We examined whether central endogenous AVP is also involved in the control of body fluid homeostasis. To explore this possibility, we examined neuronal activity in the paraventricular nucleus of the hypothalamus (PVN), periventricular parts of the PVN and limbic brain areas, as well as AVP mRNA expression in the PVN and the peripheral secretion of AVP after central salt-loading in rats that had been pretreated i.c.v. with the AVP V₁ receptor antagonist OPC-21268. Neuronal activity in the PVN evaluated in terms of Fos-like immunoreactivity (FLI), especially in the parvocellular subdivisions, was suppressed. On the other hand, FLI was enhanced in the lateral septum, the bed nucleus of the stria terminalis and the anterior hypothalamic area. Similarly, AVP mRNA expression was enhanced in the magnocellular subnucleus of the PVN, despite the lack of a significant difference in the peripheral AVP level between OPC-21268- and vehicle-pretreated groups. We recorded renal sympathetic nerve activity (RSNA) as sympathetic nerve outflow during central salt-loading. The suppression of RSNA was significantly attenuated by i.c.v. pretreatment with OPC-21268. These results suggest that the suppression of RSNA during central salt-loading might be the result of a decrease in neuronal activity in the parvocellular subdivisions of the PVN via the inhibitory action of central endogenous AVP. The parvocellular and magnocellular neurones in the PVN might show different responses to central salt-loading to maintain body fluid homeostasis as a result of the modulatory role of central endogenous AVP.     

Hormonal Activation of Female Sexual Behavior is Accompanied by Hypothalamic Norepinephrine Release

The present study employed the intracranial microdialysis technique to measure norepinephrine release in the ventrolateral dendritic fields of the ventromedial hypothalamus of freely-moving animals before and during ovarian steroid (estradiol and progesterone) activation of female sexual behavior (lordosis). One day after implantation of a dialysis probe, animals were injected with 3 μg of estradiol benzoate followed 44 h later by 200 μg of progesterone. Introduction of a male rat 4 h after progesterone treatment was correlated with dramatic increases in extracellular norepinephrine levels measured in dialysates of the ventrolateral ventromedial hypothalamus of female rats which displayed high levels of lordosis behavior. In contrast, female rats given the same steroid treatment but which did not show lordosis responses did not have elevated norepinephrine levels in their dialysates. Moreover, animals that received an estrogen antagonist concurrently with the estrogen treatment had neither an increase in ventromedial hypothalamic levels of norepinephrine during behavior testing nor did they display lordosis. These results indicate a close relationship among ovarian steroids, noradrenergic transmission in the ventromedial hypothalamus, and the expression of female sexual behavior.