Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats.

Endocrine responses to noise stress and anxiety-related behaviors were measured in groups of ovariectomized, estradiol-treated female rats given central infusions of oxytocin. Control animals receiving isotonic saline showed a large increase in plasma corticosterone concentrations in response to 10 min of white noise. This response to noise stress was significantly and dose dependently decreased by oxytocin administered intracerebroventricularly at 10 or 100 ng/h for 5 days. Oxytocin also significantly decreased rearing behavior during this stress. When a second noise stress was given 3 days after cessation of oxytocin infusion, corticosterone responses did not differ between the control and previously oxytocin-infused animals. Administration of vasopressin had no significant effect on either the corticosterone or behavioral responses to noise stress. Anxiety-related behaviors were measured on the elevated plus-maze. No significant differences were seen in maze exploration between saline- and oxytocin-treated animals when housed and tested in the same environment. However, when animals were mildly stressed by testing in an unfamiliar environment, oxytocin-treated animals showed a higher proportion of open arm entries and spent significantly more time in the open arms of the maze. Thus, oxytocin exerts a central anxiolytic-like effect on both endocrine and behavioral systems and could play a role in moderating behavioral and physiological responses to stress.

Nitric oxide modulates the release of vasopressin from rat hypothalamic explants.

The enzyme nitric oxide (NO) synthase is present in the paraventricular nucleus, while nitric oxide has recently been shown to inhibit the stimulated release of corticotrophin-releasing hormone (CRH) in vitro. Thus the possible role of NO in regulating, vasopressin (AVP), which also plays an important role in pituitary-adrenal activity, has been investigated. The effects were studied of the NO donors, L-arginine, syndnonimine-1 (SIN-1) and sodium nitroprusside, on both the basal and stimulated release of AVP, employing a previously validated system. Rat hypothalami were incubated in either medium alone or medium containing the test substances and hormone release was measured by RIA. The effect of L-arginine in the presence of the NO synthase inhibitor, L-NMMA, was also investigated. L-arginine reduced KCl-evoked AVP release; this effect was reversed by L-NMMA and reduced by the addition of ferrous human Hb. Similarly, SIN-1 and sodium nitroprusside attenuated KCl-evoked AVP release. L-arginine also reduced IL-1 beta-stimulated AVP release. NO appears to directly and specifically inhibit the stimulated release of AVP from rat hypothalamic explants in vitro, similar to its effects on CRH. These findings provide further evidence that NO may be involved in neuroendocrine regulation.

The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses.

The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 +/- 0.4 pulses between 1700-2300 h vs. 5.3 +/- 0.8 pulses between 0500-1100 h; P < 0.05) and height (198 +/- 27 ng/ml between 1700-2300 h vs. 107 +/- 14 ng/ml between 0500-1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 +/- 67 ng/ml; Fischer, 390 +/- 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to i.v. CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 +/- 95 ng/ml) compared with 30 min (390 +/- 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.

Ultradian rhythm of basal corticosterone release in the female rat: dynamic interaction with the response to acute stress.

The present study investigated the dynamic regulation of the hypothalamo-pituitary-adrenal axis and its significance to acute stress responsiveness in the female rat. An automated, frequent blood-sampling technique allowed the circadian rhythm of corticosterone to be resolved into a series of pulses. These were equally distributed (mean interval, 50.9 +/- 3.7 min) throughout the 24-h cycle, but their magnitude varied significantly, being higher between 1800-2200 h (137 +/- 9 ng/ml) than between 0600-1000 h (75 +/- 17 ng/ml). This pattern of release indicates continuous, but variable, activity of the axis throughout the day. The pulsatile ultradian rhythm suggested alternate periods of secretion and inhibition, which were found to have a profound effect on the corticosterone responses to acute stress. Noise stress (10 min, 114 decibels) evoked a transient increase in corticosterone, which reached a maximum (377 +/- 87 ng/ml) 20 min after onset. However, within this group (n = 26) the response varied depending on the underlying basal activity. When stress coincided with a rising (secretory) phase of a pulse, corticosterone concentrations rose to 602 +/- 150% of mean basal concentrations (P < 0.001). In contrast, when stress coincided with a falling (nonsecretory) phase of a pulse, a significantly smaller response, no greater than a basal pulse, was evoked. Thus, the alternate periods of secretion and inhibition generating basal hypothalamo-pituitary-adrenal activity are an important determinant of responses to acute stress.

Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation.

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA responses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.

Lack of effect of protein deprivation-induced intrauterine growth retardation on behavior and corticosterone and growth hormone secretion in adult male rats: a long-term follow-up study.

To further define the neuroendocrine consequences of intrauterine growth retardation (IUGR), we have used a rat model of maternal protein restriction throughout pregnancy to examine the pattern of corticosterone and GH secretion under basal conditions and in response to psychological stress in male offspring at 4, 9, and 18 months of age. The findings were correlated with studies of behavioral activity. Despite a consistent reduction in birth weight and failure of catch-up growth, there were no significant differences in GH secretory profiles between IUGR and control rats at any age. We were unable to demonstrate a difference in the number, amplitude, length, or area of corticosterone secretory pulses between control and IUGR animals; although again, there was a significant decrease with age. The mean peak plasma concentration of corticosterone in response to a noise stress also declined with age but was unaffected by IUGR. There were no consistent, statistically significant differences in behavioral responses between normal control and IUGR animals or between groups of animals at different ages. These results do not, therefore, support the presence of major functional abnormalities in either GH or corticosterone secretory responses in adult male rats subjected to IUGR.

Physical and sexual abuse and associated mental disorders among alcoholic inpatients.

OBJECTIVE: The purpose of this study was to investigate the adult psychiatric correlates of childhood abuse among alcoholic inpatients. METHODS: The 802 patients, who included 321 women, were admitted to one of five New York State alcohol treatment inpatient centers. Each patient was interviewed, and sexual and physical abuse history, DSM-III diagnosis, and other characteristics were recorded. RESULTS: The overall prevalence of reported childhood abuse was 59% for women and 30% for men. Family history of alcoholism was associated with higher levels of physical and sexual abuse. Gender differences in types of childhood abuse (i.e., sexual abuse only, physical abuse only, dual abuse) were evident; 49% of the women and 12% of the men reported sexual abuse (with or without physical abuse), 33% of the women and 24% of the men reported physical abuse (with or without sexual abuse), and 23% of the women and 5% of the men reported dual abuse. Abuse status, and especially dual abuse, was associated with higher rates of antisocial personality disorder and suicide attempts among women and men, with generalized anxiety disorder among women, and with major depression among men. CONCLUSIONS: The findings highlight the long-term associations between sexual and physical abuse and adult coexisting mental disorders among alcoholic inpatients. Addressing unresolved intrapsychic trauma associated with childhood abuse may increase the efficacy of treatment outcomes and reduce relapse rates among alcoholics.

Renal responses to oxytocin during the 4 days of the oestrous cycle in the rat.

Oxytocin was administered to virgin female rats at doses of 25-200 pmol/min during 0.077 mol NaCl/l infusion at 150 microliters/min on each day of the oestrous cycle. The resultant rates of urine flow, glomerular filtration (GFR) and electrolyte excretion were determined. Oxytocin caused significant increases in urine flow (P < 0.001) and sodium excretion (P < 0.001); both responses being dose-dependent (P < 0.02 and P < 0.01 respectively). Significant variations in the renal responsiveness to the hormone occurred over the 4 days of the oestrous cycle. On oestrus the lowest dose of 25 pmol oxytocin/min produced a significant increase in urine flow (from 139.5 +/- 4.3 to 165.6 +/- 7.1 microliters/min, P < 0.005) and a dose of 50 pmol/min produced a significant increase in sodium excretion (from 10.6 +/- 0.1 to 14.5 +/- 0.7 mumol/min, P < 0.005). Significant increases in urine flow and sodium excretion were seen on pro-oestrus with hormone administration rates of 50 and 100 pmol/min respectively and on dioestrus day 2 with a rate of 100 pmol/min. On dioestrus day 1 no increase in urine flow or sodium excretion was seen over the dose range of oxytocin administration. A dose of 100 pmol oxytocin/min significantly increased GFR on pro-oestrus and dioestrus day 2, but not on the other 2 days of the cycle. The circulating hormone concentrations produced by oxytocin infusion were similar on each day of the cycle and so could not account for the differences seen. Therefore, these results suggest varying renal responsiveness to oxytocin during the reproductive cycle of the female rat.

Variations in oxytocin secretion during the 4-day oestrous cycle of the rat.

Oxytocin concentrations in the plasma, pituitary and hypothalamus of female rats were determined in the morning and evening over the 4-day oestrous cycle. Vasopressin concentrations were also determined to allow calculation of the ratios of the two hormones. The results were compared with those from male rats. Plasma oxytocin concentrations were significantly higher in the evening than in the morning on the day of oestrus. Although the evening concentration achieved was similar on each day of the cycle, morning plasma oxytocin concentrations showed a progressive rise from oestrus to pro-oestrus so that no significant diurnal increases were observed on the other days of the cycle. Vasopressin concentrations in the plasma were also seen to increase over the days of oestrus, dioestrus day 1 and dioestrus day 2. On pro-oestrus the plasma concentrations of vasopressin remained unchanged. The ratio of oxytocin:vasopressin fell during the light hours of the cycle. The hypothalamic content of both hormones showed a rise during the hours of daylight parallel to that seen in the plasma, whereas the pituitary content fell over the same period. The diurnal pattern of hormone release observed in male rats was similar to that in females at oestrus. However, the plasma oxytocin concentrations were significantly higher in the male. The plasma clearance rate of vasopressin did not vary significantly during the oestrous cycle. However, the plasma clearance rate for oxytocin did show significant variation, being highest on dioestrus day 1 and lowest on dioestrus day 2.

The influence of reproductive status on vasopressin release in the rat.

It has been shown that surgical ovariectomy of the rat results in a fall in plasma vasopressin concentrations suggesting that ovarian steroids may influence hormone release. To determine whether a similar fall is found on suppression of the oestrous cycle, vasopressin concentrations were monitored after treatment with the antioestrogen preparation tamoxifen or a long-acting analogue of LH-releasing hormone (LHRH) which suppresses ovarian function. Treatment with either agent was found to result in a fall in circulating vasopressin concentrations, with little effect on fluid balance. To determine whether the ovary could influence the vasopressin release in response to known stimuli, hormone concentrations were measured in ovariectomized animals during extracellular fluid hypertonicity produced by an i.p. injection of hypertonic saline and hypovolaemia produced by an i.p. injection of polyethylene glycol. It was found that after ovariectomy or treatment with tamoxifen, the response to hypertonicity was unaffected but that to hypovolaemia was attenuated. Treatment with LHRH affected the response to both hypovolaemia and hypertonicity.

The natriuretic actions of vasopressin in the female rat: variations during the 4 days of the oestrous cycle.

The renal actions of vasopressin were studied in the conscious female rat. Vasopressin caused a dose-dependent increase in sodium excretion when administered at 40-160 pmol/min. The highest dose, which increased sodium excretion from 10.4 +/- 0.3 mumol/min (n = 32) to 18.3 +/- 0.8 mumol/min (n = 8, P < 0.001), also caused a significant rise in glomerular filtration rate (GFR). The antidiuretic and natriuretic responses to vasopressin varied significantly over the 4 days of the oestrous cycle. Both responses were greatest on pro-oestrus, being -57 +/- 3 and 52 +/- 3% above the control values with 80 pmol vasopressin/min. Responses of similar magnitude were also seen on dioestrus day 1. On these two cycle days the effects on urine flow and sodium excretion were accompanied by a significant increase in GFR. Smaller antidiuretic and natriuretic responses were seen on oestrus and dioestrus day 2, without concomitant changes in GFR. As the plasma vasopressin concentrations produced by hormone infusion were similar on each day of the cycle, the renal responsiveness to vasopressin appears to vary over the 4 days of the oestrous cycle. This may be important in terms of alteration and possible disturbances of fluid balance which may occur during reproductive cycles and pregnancy.

Do vasopressin and oxytocin have synergistic renal effects in the conscious rat?

The renal effects of arginine vasopressin and oxytocin were studied in the conscious unrestrained rat infused with 0.077 M NaCl. Peptides were infused at rates of 24 and 160 pmol/min (vasopressin) or 30 and 200 pmol/min (oxytocin) either alone or as a combination of the two lower or two higher doses. The rates of infusion were selected to give ratios of oxytocin:vasopressin similar to those seen in the plasma of euhydrated and dehydrated rats. Vasopressin produced dose-dependent antidiuretic and natriuretic responses, the natriuresis commencing after 15-30 min infusion. Oxytocin produced dose-dependent diuretic and natriuretic responses, the natriuresis commencing within the first 15 min of infusion. Combined infusion of vasopressin and oxytocin produced dose-dependent antidiuretic responses which were comparable to those seen with vasopressin alone. The natriuretic response from combined infusion at the higher rate appeared to have the greater magnitude for individual 15-min periods of the vasopressin response combined with the longer duration of the oxytocin response. Although the total natriuretic response was therefore greater, this difference failed to reach significance. Only the higher rates of infusion of vasopressin and oxytocin significantly increased the clearance of sodium, by 53 +/- 23 and 62 +/- 18% and glomerular filtration rate (GFR) by 23 +/- 4 and 23 +/- 4% respectively. The clearance of sodium during the combined hormone infusion was significantly greater (109 +/- 21%), while the rise in GFR at 23 +/- 5% was comparable to that seen when each hormone was given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Daily rhythms in the hormone content of the neurohypophysial system and release of oxytocin and vasopressin in the male rat: effect of constant light.

Patterns of neurohypophysial hormone secretion and changes in the hormone content of the hypothalamus and posterior pituitary lobe were monitored in the male rat for cycles of 24 h in association with changes in food and water intake and fluid excretion. Plasma oxytocin and vasopressin concentrations were seen to rise significantly over the hours of daylight, decreasing during the night. Parallel changes were seen in the immunoreactive material in the hypothalamus, whilst the content of the neurohypophysis was inversely related to plasma concentrations. The ratio of plasma oxytocin:vasopressin reached a significant peak at about 02.00 h which might be related to the feeding activity of the rats, food and water intake being largely confined to the night, as was fluid excretion. On exposure to constant light, despite initial disruption hormonal rhythms were still seen but showed a phase shift. The relationships between plasma and tissue levels were maintained. Patterns of food and water intake and urinary excretion were little affected by exposure to constant light, remaining largely confined to the former night phase. The hormonal rhythms appeared to be more closely related to the activity of the rats, which also showed a phase shift during constant light.

Effect of oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin in the rat.

The effect of three oxytocin receptor antagonists on the renal actions of oxytocin and vasopressin was investigated in conscious male rats infused with hypotonic saline. Infusion of oxytocin at 100 pg/min produced plasma concentrations of 12.7 +/- 3.3 pmol/l and led to significant increases in sodium excretion, urine flow and glomerular filtration rate (GFR). The increase in sodium excretion of 42 +/- 9% during oxytocin infusion was significantly decreased by all three antagonists to 15 +/- 5% (10 ng [mercapto-proprionic acid1, D-Tyr(Et)2,Thr4,Orn8]-oxytocin/min), 13 +/- 5% (5 ng desGly9[D-Trp2,Thr4,Orn8]-dC6oxytocin/min) and 4 +/- 5% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/min). Similarly, the increase in urine production of 22 +/- 5% associated with oxytocin infusion was significantly decreased to 4 +/- 3% (5 ng desGly9[D-Trp2,D-Thr4,Orn8]-dC6 oxytocin/min) and 1 +/- 4% (1 ng d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr(NH2)9]-vasotocin/ min). All three antagonists blocked the oxytocin-induced increase in GFR when infused at 10 ng/min. Infusion of vasopressin at 160 pg/min produced plasma concentrations of 10.1 +/- 2.1 pmol/l and this led to a significant increase in sodium excretion and a significant decrease in urine flow rate. None of the antagonists had any effect on the natriuretic or antidiuretic actions of vasopressin suggesting that different receptors are involved in these renal actions of the two peptides.

The effect of vasopressin and oxytocin on glomerular filtration rate in the conscious rat: contribution to the natriuretic response.

Urine flow, sodium excretion, mean arterial blood pressure and glomerular filtration rate (GFR) were determined in the conscious unrestrained rat infused with hypotonic saline. The effects of vasopressin infused at 24 and 160 pmol/min and oxytocin infused at 30 and 200 pmol/min were determined. The lower doses of each hormone gave plasma concentrations within the physiological range whereas the higher doses produced plasma concentrations equivalent to those seen following dehydration. Vasopressin produced dose-dependent antidiuretic and natriuretic responses. Hormone infused at both rates increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. Fractional excretion of sodium was significantly elevated by both doses. Oxytocin produced dose-dependent diuretic and natriuretic responses. Again both rates of infusion increased the clearance of sodium, but only the higher dose caused a significant increase in GFR. The lower dose caused a significant increase in the fractional excretion of sodium. It appears, therefore, that increases in GFR may have a role in the natriuretic response to both hormones. However, this response can also be seen when GFR remains unchanged. This fact, together with the observed increases in the fractional excretion of sodium, indicates that these hormones have additional tubular actions.

Influence of oxytocin on sodium excretion in the anaesthetized Brattleboro rat.

The contribution of oxytocin to the maintenance of renal Na+ excretion in the Brattleboro rat has been examined in animals infused with hypotonic saline. Brattleboro rats exhibited hypernatraemia and hyperosmolality associated with greatly increased plasma concentrations of oxytocin by comparison with Long-Evans control rats. Neurohypophysectomy to remove the secretion of the remaining posterior pituitary peptide, oxytocin, led to greatly diminished rates of Na+ excretion in the Brattleboro rat. Oxytocin replacement to achieve plasma levels equivalent to those in intact Brattleboro rats produced a substantial and sustained natriuresis in the neurohypophysectomized animal. Oxytocin secretion evoked in response to saline infusion would thus appear to be effective in promoting renal Na+ excretion in the absence of vasopressin in the Brattleboro rat.

Patterns of neurohypophysial hormone release during dehydration in the rat.

A study was performed investigating the daily patterns of hormone release accompanying changes in fluid balance in the male rat during 48 h of dehydration. The blood volume decreased by 18%, the largest change occurring during the initial period when the rats showed an effective loss of body sodium. During the second day of dehydration, sodium retention was again seen. Plasma sodium concentrations showed a progressive increase, the total rise being 5-6%; the greatest changes were seen during the dark phases of the cycle which may be due to the nocturnal food intake. Plasma vasopressin and oxytocin concentrations were significantly elevated throughout dehydration to levels which could be reproduced by acutely increasing plasma sodium and decreasing blood volume to the same extent. The observed increases were influenced by the phase of the day-night cycle, being greatest over the dark phases of the cycle. The overall increases were greatest when dehydration commenced at the start of the dark phase. Dehydration initially led to a rise in plasma corticosterone concentrations, whilst plasma concentrations of atrial natriuretic peptide were decreased. Plasma angiotensin II concentrations rose significantly during the later period of sodium retention.

Significance of pulsatility in the HPA axis.

A stress-free automated blood sampling system has been employed to demonstrate pulsatile hypothalamo-pituitary-adrenal (HPA) activity in the rat. In females, pulses of corticosterone secretion occur approximately once/hour throughout the 24 h cycle, with variation in pulse amplitude underlying a diurnal rhythm. Males show smaller pulses of secretion which become widely spaced during the early light phase nadir. Ageing does not affect the occurrence of pulses but the diurnal variation is lost. Analysis of the relationship between the HPA response to an acute noise stress and its coincidence with the various phases of the pulse, suggests that pulsatile activity arises from alternating periods of activation and suppression. Responses to i.v. corticotropin-releasing factor are not affected by pulse phase, indicating that this relationship is not generated at the pituitary-adrenal level. This phase relationship holds for all strains of rat except the hyperresponsive Fischer-344 in which an exaggerated stress response arises from a lack of phase-dependent suppression. Patterns of pulsatile activity are also modulated by neonatal programming or chronic HPA activation arising from adjuvant-induced arthritis, with consequent impact upon the response to acute stimuli. Thus, variations in the patterns of pulsatile activity are important determinants of both basal secretion and acute responses of the HPA axis.

Peripartum plasticity within the hypothalamo-pituitary-adrenal axis.

The hypothalamo-pituitary-adrenal (HPA) axis plays important roles in the adaptive changes in physiology that occur during pregnancy and lactation. Although the axis still exhibits a pulsatile pattern of secretion, the normal diurnal rhythm of pulse amplitude is lost during lactation, such that mean basal levels remain constant throughout the day. In addition, the peripartum period is associated with a remarkable plasticity in stress-induced HPA activity, in that the increase of HPA activity normally seen in response to either physical or psychological stresses in the non-reproductive state become severely attenuated or absent in the lactating animal. This stabilization of both basal and stress-induced HPA activity may be important for maintaining a constant endocrine environment, thereby preventing any programming effects on the developing offspring. Attenuation of the stress response is initiated in late pregnancy and is temporally associated with luteolysis, indicating possible steroid hormone involvement. Indeed, mimicking the luteolytic changes in oestrogen and progesterone levels in non-pregnant animals induces a similar attenuation of the stress response. Furthermore down-regulation of the stress response is, at least in part, centrally mediated since in the period following luteolysis rats will show a decreased level of stress-induced neuronal activation of the PVN, as measured by the expression of either c-fos or CRH mRNAs. Persistence of this adapted state is dependent upon the continued suckling stimulus, as removal of the offspring litter rapidly leads to resumption of HPA responses to and the appearance of an exaggerated diurnal rhythm. The underlying mechanisms responsible for this stress hyporesponsiveness may include plasticity of noradrenergic and oxytocin pathways. In view of its role in other reproductive behaviors, a stress-inhibiting effect of oxytocin may reflect a more widespread co-ordinating role in the peripartum animal.

The effect of pinealectomy on osmotically stimulated vasopressin and oxytocin release and Fos protein production within the hypothalamus of the rat.

Osmotically stimulated vasopressin and oxytocin release were measured in pinealectomized and sham operated male rats infused with hypertonic sodium chloride. Neuronal activation in the hypothalamic regions associated with oxytocin and vasopressin release was investigated by quantitative assessment of Fos protein production. The osmotically stimulated release of both vasopressin and oxytocin was significantly lower in pinealectomized animals as compared to sham operated controls. The slope of regression lines between plasma osmolality and hormone concentrations in the sham animals showed a 1.0 +/- 0.1 pmol per mosm/kg rise in vasopressin and 2.0 +/- 0.4 pmol per mosm/kg rise in oxytocin whilst in the pinealectomized animals these values were significantly lower at 0.4 +/- 0.1 pmol vasopressin per mosm/kg and 0.8 +/- 0.2pmol oxytocin per mosm/kg. The osmotic thresholds for hormone release were unaffected by pinealectomy. Fos production was also significantly lower in the supraoptic nucleus and organ vasculosum of the lamina terminalis in the pinealectomized rat at 62 +/- 20 and 59 +/- 9 Fos immunoreactive cells/section as compared to corresponding values of 202 +/- 31 and 123 +/- 20 Fos immunoreactive cells/section in the shams. These observations suggest that reduced hormone release in the pinealectomized animal is due to lowered responsiveness of central osmoregulatory mechanisms and that melatonin may therefore influence the activation of the magnocellular system.