Effects of electroconvulsive therapy on plasma vasopressin and oxytocin

BACKGROUND: Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients. METHODS: Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed. RESULTS: The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT (ps < .01-.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature. CONCLUSIONS: Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.     

Effects of oxytocin on in vitro ovarian contractility during the estrous cycle of the rat

Necrotizing skin lesions developed in a man with chronic ulcerative colitis. No evidence of intrinsic disease of medium or small-sized vessels was found. A circulating cryofibrinogen was thought to be responsible for in situ thrombosis leading to skin infarctions. Sodium warfarin in a daily dose of 2.5 to 5 mg appears to have thwarted progression of developing lesions and the occurrence of new ones.     

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.     

Thyrotropin-releasing hormone affects the oxytocin, vasopressin and prolactin release in female rats during midlactation: relation to suckling

The effect of thyrotropin-releasing hormone (TRH; 200 ng i.c.v.) on oxytocin (OT), vasopressin (AVP) and prolactin (PRL) release was estimated in female Wistar rats during midlactation. The hypothalamo-neurohypophysial radioimmunoassayed OT and AVP storage as well as blood plasma level of both neurohypophysial hormones and PRL in females suckled or not suckled have been studied. I.c.v. administration of TRH increased AVP content both in the hypothalamus and neurohypophysis of suckled females; however, plasma AVP level did not change. TRH increased the hypothalamic as well as neurohypophysial OT content during suckling. Simultaneously, TRH inhibited OT release into the blood plasma. On the contrary, in not suckled females TRH increased OT plasma concentration. I.c.v. TRH raised the PRL concentration in plasma of lactating but, at the moment, not suckled females. On the contrary, i.c.v. TRH injection into females just suckled was followed by a decrease in PRL plasma level. TRH probably acts in the central nervous system as an inhibitory neuromodulating factor for the vasopressin release. Also, it cannot be excluded that TRH--otherwise known to enhance the PRL release--suppresses the oxytocin-prolactin positive feedback mechanism when activated temporarily by suckling.     

Hypothalamic and neurohypophysial vasopressin and oxytocin content as influenced by haemorrhage in melatonin-treated male rats

The effect of haemorrhage (1 ml per 100 g b. w.) on the vasopressin and oxytocin storage in the hypothalamus and neurohypophysis of melatonin-treated male rats was determined. Melatonin treatment (100 micrograms/100 g b. w., once daily over 8 days) resulted in a known decrease of vasopressin as well as oxytocin content both in the hypothalamus and neurohypophysis. Haemorrhage decreased the neurohypophysial vasopressin and oxytocin storage in animals injected with vehicle solution or otherwise not treated. In melatonin-treated rats, however, bleeding did not affect the actual (i.e., decreased by melatonin) vasopressin and oxytocin content in the hypothalamo-neurohypophysial system. The results demonstrate that melatonin may be involved in mechanisms determining the rate of the response of vasopressinergic and oxytocinergic neurones to bleeding.     

Presence of melatonin in plasma and urine or pinealectomized rats

Melatonin was shown to occur in rat plasma and urine after pinealectomy by bioassay, radioimmunoassay, and thin-layer chromatography. Total daily excretion of melatonin in pinealectomized rats was about 20% of control. Light-dark rhythms of plasma melatonin levels and urinary excretion rates disappeared after pinealectomy.     

Effects of central oxytocin administration on intraoral intake of glucose in deprived and nondeprived rats

We evaluated the effects of lateral intracerebroventricular administration of oxytocin (OT) and/or a selective oxytocin-receptor antagonist (OTX), 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-OT, on ingestion of intraorally delivered 12.5% glucose in rats that were either nondeprived or deprived of food for 20 h. In deprived rats, OT delivered 30 min before an initial intake test yielded a dose-related reduction of intraoral glucose intake. The highest dose tested, 20 nmol, reduced intraoral glucose intake by 45%. The effect was short-lived, however. Intraoral intake for a second test, initiated 60 min after the termination of the first, increased as a function of OT dose so that total session intake was unaffected by OT treatment. The suppression of intraoral intake by 20 nmol OT was reversed by pretreatment (45 min before testing) with OTX. In nondeprived rats, by contrast, OT yielded no effect on first-test, second-test, or total session intakes. Significant increases in first-test and total session intakes were obtained when OTX (20 nmol) was administered alone both in deprived (32% increase in first-test intake) and nondeprived (31% increase) rats. In general, the results obtained are consistent with the suggestion that OT contributes to the control of meal size and, in particular, to the process of satiation, which is the aspect of ingestive control highlighted by the specialized intake test used in the present study.     

Effects of gonadal steroid hormones on hypothalamic vasopressin mRNA level in male and female rats

Experiments were carried out in 10-11-week old gonadectomized male and female Sprague-Dawley rats. Dot-blot analysis and 3'-end digoxigenin-labeled 26 meroligonucleotide probe was used in detecting the mRNA level hypothalamic vasopressin (AVP). The basal hypothalamic AVP-mRNA level in the sham-operated intact males was 45% higher than that in the sham-operated intact females (P < 0.05). Plasma osmolality was also higher in the sham-operated intact males than in the sham-operated intact females (P < 0.05). The hypothalamic AVP-mRNA level in ovariectomized rats was 30% higher than that in sham-operated intact females (P < 0.05). Although the hypothalamic AVP mRNA level tended to be lower in castrated males than in sham-operated intact males, the difference was not statistically significant. The difference in plasma osmolality between gonadectomized males and females was statistically insignificant. In castrated males, hypothalamic AVP-mRNA level was decreased following sc injection of estradiol (P < 0.05), but testosterone, progesterone or a combination of estradiol and progesterone were without effect. In ovariectomized rats, sc injection of estradiol or a combination of estradiol and progesterone resulted in a decrease in hypothalamic AVP-mRNA level (P < 0.01), but progesterone or testosterone had no effect. The difference in plasma osmolality between gonadal steriod hormones-treated rats and vehicle-treated rats was not statistically significant. These findings indicate that gonadal steriod hormones can affect hypothalamic AVP-mRNA level in rats, through some central mechanism.     

Effects of age on cerebrospinal fluid oxytocin levels in free-ranging adult female and infant rhesus macaques.

There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of infants. The main goal of this study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on Cayo Santiago, PR. CSF oxytocin levels were examined in relation to individuals' demographic and reproductive characteristics as well as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7–26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38–134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. These findings: 1) provide feasibility data for examining CSF oxytocin levels in free-ranging non-human primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Research is now required to examine CSF oxytocin levels in the context of social functioning in free-ranging rhesus monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of methylphenidate on underachieving children.

Compared the reactions of 28 6-9 yr old underachieving children to active drug and placebo treatments. Mean drug dosage was 21.07 mg/day. In a double-blind, counterbalanced design, each treatment condition was maintained for 12 wks. Using multiple medical and psychological measures (e.g., TAT, WISC, and Bender-Gestalt), as well as a full length, standardized achievement test (Iowa Test of Basic Skills) and behavior ratings, the typical suppressive behavioral effects were observed. No substantial drug effects on achievement were found, and pretreatment evaluations failed to support the common assumption of concomitance among hyperactivity, minimal brain dysfunction, and learning disorder. Reduced responsivity on active drug treatment was observed clinically. It is urged that effects of methylphenidate hydrochloride (Ritalin) on specific functions be considered rather than global effects without specifications, and it is concluded that Ritalin should not be used to "treat" learning disorders. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions of the light-dark cycle, adrenal glands and time of steroid administration in determining the temporal sequence of LH and prolactin release in female rats

The purpose of this study was to determine the effects of the light-dark cycle, adrenal glands and steroid treatment schedule on LH and prolactin release in rats. Rats maintained in either a 14 h light: 10 h dark schedule (LD) or constant illumination (LL) were ovariectomized (Ovx) or ovariectomized and adrenalectomized (Ovx-Adx). Three weeks later at 1000 h, animals received a SC injection of estradiol benzoate (EB 10 mug/100 g BW) or oil. Three days after EB administration, rats were given a 2 mg injection of progesterone (P) or oil at either 0200, 0500, or 0900 h, and were sequentially bled at four-hour intervals until 1700 h. P administered at all three times increased the amplitude of the plasma LH surge and advanced it, though by no more than 4 hours, in LD. In LL, P was more effective in advancing the time of LH release, although peak plasma LH levels were considerably less than those observed in LD. Adrenalectomy increased the sensitivity of Ovx rats to the effects of EB and P on LH release. P administration at either 0200, 0500 or 0900 h advanced prolactin release in EB-primed Ovx and Ovx-Adx in LL and LD, but only in LL did P increase the amplitude of the plasma prolactin surge. The lighting conditions did not alter the effectiveness of P in advancing prolactin release. Our study demonstrates that the light-dark cycle and adrenal steroids interact to synchronize the timing of LH release in rats, but the regulatory mechanism controlling prolactin release is less strictly cued to these environmental factors.     

Plasma-corticosterone levels during active-avoidance learning in rats.

Assessed the pituitary-adrenal function of 17 male Moll-Wistar rats during shuttle-box avoidance learning by determining plasma-corticosterone levels following the initial avoidance-training session, a session during the acquisition phase (when 80% performance rate was attained), and a session late in asymptotic performance. A slight but significant decrease in the postsession level occurred between the initial and acquisition phases, while a much larger decrease occurred by the last sampling session when the behavior was stabilized. The occurrences of electric shocks did not predict the magnitude of the corticosterone elevations in the acquisition or stabilized phases. In the stabilized phase, plasma corticosterone was negatively correlated with the amount of intertrial time spent in sniffing and grooming. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stationary organotypic cultures of oxytocin and vasopressin magnocellular neurones from rat and mouse hypothalamus

Rat and mouse hypothalami from postnatal animals containing highly differentiated neurones survive very well in long-term (>15 days in vitro, DIV) stationary organotypic cultures. Magnocellular oxytocin (OT) and vasopressin (VP) neurones are present in identifiable paraventricular (PVN), supraoptic (SON) and accessory (ACC) nuclei in these cultures. After 15 DIV in standard medium immunocytochemistry revealed 427 +/- 63 OT cells and 217 +/- 27 VP cells per cultured rat hypothalamus, and 380 +/- 72 OT cells and 622 +/- 91 VP cells per cultured mouse hypothalamus. Following a 7-day adaptation period in standard culture medium containing serum, the rat slice-explants survived very well after subsequent transfer to defined, serum- free media (SFM) for an additional 8 days. The number of OT cells surviving in SFM was 612 +/- 147 OT cells per cultured rat hypothalamus. Only 0.5% of the magnocellular OT and VP neurones in the cultures appeared to express both peptides. Experiments on c-fos gene expression in these cultures showed that while only 12% of the magnocellular OT and VP neurones contained barely detectable Fos protein in their nuclei under control conditions, potassium depolarization of these cultures for 3 h produced intense c-fos expression in 87-91% of these cells. Thus, magnocellular neurones in these cultures are sufficiently stable and responsive to permit long-term physiological and gene expression studies to be done under defined media conditions.     

Neuropsychological performance and plasma cortisol, arginine vasopressin and oxytocin in patients with major depression

Understanding the nature of swallowing in persons without swallowing problems is a prerequisite to evaluating the nature and extent of dysphagia in persons with compromised swallowing. In order to determine how swallowing varies with age and with liquid bolus volume in women, we assessed 167 normal female swallowers videofluoroscopically and obtained multiple measures of swallowing function. The women in this study demonstrated a change in swallowing function with age, due primarily to an increase in pharyngeal transit and total duration of the motor response. The duration of closure and opening of valves in the upper aerodigestive tract also increased with age, and the duration of laryngeal elevation and hyoid movement peaked in the 60-79-year-old age groups. Bolus volume effects were quite consistent across most measures. As the bolus volume increased from 1 ml to 10 ml, transit times decreased and durations of valve closure and opening increased. The results of this study may be used to specify the relationship of swallowing function to age and liquid bolus volume in women, relationships that heretofore have been observed only in part and in smaller and more heterogeneous populations.     

Design, synthesis and some uses of receptor-specific agonists and antagonists of vasopressin and oxytocin

Selective agonists and antagonists are powerful tools for studies on AVP and OT receptors and on the physiological and pathophysiological roles of AVP and OT. Here we show how some of these peptides and their radiolabelled derivatives were designed. We also present examples of the currently available cyclic and linear OT and AVP agonists and antagonists from our laboratories.     

Effect of hepatic vagotomy on plasma insulin levels during fasting in rats

The present investigation was designed to evaluate the effect of a selective hepatic vagotomy (HV) on the insulin response in rats fasted for 24 h when blood glucose levels were or were not maintained by a constant glucose infusion. Rats were divided into three dietary groups: one group of normally fed rats, one group of 24-h fasted rats, and one group of 24-h fasted rats infused with glucose throughout the fasting period. Each of these groups was subdivided into HV and sham-operated (SHM) rats. Fasting without glucose infusion resulted in a significant (p < 0.05) decrease in plasma glucose, liver glycogen, and insulin concentrations and in a significant (p < 0.01) increase in beta-hydroxybutyrate and FFA concentration. Despite the maintenance of plasma glucose concentrations in the glucose-infused groups, the concentrations of liver glycogen and insulin were still decreased (p < 0.01) and the concentrations of beta-hydroxybutyrate were still increased (p<0.05) at the end of the fasting period. However, no significant differences in insulin or in beta-hydroxybutyrate concentration were found between HV and SHM rats. It is concluded that the decline in plasma glucose concentration during fasting does not totally explain the insulinopenic response to fasting, and that the liver, through the mediation of the hepatic vagus nerve, does not seem to contribute to insulinopenia in 24-h fasted rats.     

Effects of situational complexity and repeated testing on rats'' behaviour in a light-dark preference situation

The nature of the epinephrine action on the excitability of giant neurons depends on its concentration. With a concentration of 1-10(-5) M changes in electrophysiological parameters of the somatic neurons membrane produced by its bore proof to the rising and with that of 1-10(-4) M -- to its falling excitability. Propranolol was indifferent in regard to both epinephrine effects, while dihydroergotoxin abolished the inhibitory effect of epinephrine.     

Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release

Cows from eight commercial dairies were randomly assigned to intrammamary infusions of cephapirin or cephapirin plus interleukin-2 at the end of lactation. During the first phase of the trial, interleukin-2 was administered to 159 cows at a dose of 1 mg per gland by intracisternal infusion immediately after 300 mg of cephapirin were administered. One hundred sixty-one cows received infusions of a placebo (phosphate-buffered saline; PBS) immediately after cephapirin. In the second phase of the trial, 70 cows received 2 mg of interleukin-2 per gland, and 78 cows received the placebo. Cows were observed daily by the participating farmer for 72 h after infusion and also during routine feeding and care during the dry period and at calving. Potential side effects from udder infusions, particularly gross abnormalities of the udder and signs of systemic side effects were monitored. During the first phase, cure rates for intramammary infections caused by Staphylococcus aureus that were present at the end of lactation were 33.3% for quarters treated with cephapirin and 53.6% for quarters treated with cephapirin and interleukin-2. Cure rates did not differ between treatment groups for all other pathogens or during the second phase of the trial. The incidence of new intramammary infections during the dry period was not affected by intramammary infusion of interleukin-2. Eighteen of 229 (7.9%) cows treated with interleukin-2 aborted within 49 d of treatment compared with 4 of 239 (1.7%) cows treated with PBS. Eleven of the 18 (61.1%) abortions by cows treated with interleukin-2 occurred 3 to 7 d after infusion; none of the abortions by cows treated with PBS occurred until wk 7 after infusion.