Prolactin Response Research Articles

Effects of heat acclimation on time perception

Cognitive performance is impaired during prolonged exercise in hot environment compared to temperate conditions. These effects are related to both peripheral markers of heats stress and alterations in CNS functioning. Repeated-exposure to heat stress results in physiological adaptations, and therefore improvement in exercise capacity and cognitive functioning are observed. The objective of the current study was to clarify the factors contributing to time perception under heat stress and examine the effect of heat acclimation. 20 young healthy male subjects completed three exercise tests on a treadmill: H1 (at 60% VO2peak until exhaustion at 42°C), N (at 22°C; duration equal to H1) and H2 (walk until exhaustion at 42°C) following a 10-day heat acclimation program. Core temperature (TC) and heart rate (HR), ratings of perceived fatigue and exertion were obtained continuously during the exercise, and blood samples of hormones were taken before, during and after the exercise test for estimating the prolactin, growth hormone and cortisol response to acute exercise–heat stress. Interval production task was performed before, during and after the exercise test. Lower rate of rise in core temperature, heart rate, hormone response and subjective ratings indicated that the subjects had successfully acclimated. Before heat acclimation, significant distortions in produced intervals occurred after 60minutes of exercise relative to pre-trial coefficients, indicating speeded temporal processing. However, this effect was absent after in acclimated subjects. Blood prolactin concentration predicted temporal performance in both conditions. Heat acclimation slows down the increase in physiological measures, and improvement in temporal processing is also evident. The results are explained within the internal clock model in terms of the pacemaker-accumulator functioning.

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n=46 women) participated in two morning sessions in which they received 50mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n=23) or luteal phase of the MC. Serum cortisol, salivary cortisol, prolactin, luteinizing hormone (LH), and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women.

Prolactin and natural killer cells: evaluating the neuroendocrine-immune axis in women with primary infertility and recurrent spontaneous abortion.

An association between serum prolactin (PRL) and peripheral blood natural killer (NK) cells has been described in healthy women. We explored for the first time the PRL response to the thyrotrophin-releasing hormone (TRH) test and the association between PRL and NK cells in women with reproductive failure. A total of 130 women [31 primary infertility, 69 recurrent spontaneous abortion (RSA), and 30 fertile women] were evaluated by a TRH test to analyze the following: basal PRL (bPRL), peak-time PRL, PRL absolute and relative increase, decline-time PRL. Hyperprolactinaemia (HPRL) was defined as bPRL ≥15ng/mL. NK cells were characterized by immunophenotyping. Significantly higher bPRL levels were found in the infertile women than in controls. Both the infertile and the RSA women showed significantly elevated NK levels. bPRL levels correlated with NK cells in HPRL-infertile women. In patients with HPRL, an association between NK cell and bPRL results. The dynamic test in the infertile women would help in the management of the pregnancy impairment.

Corticosterone, prolactin and egg neglect behavior in relation to mercury and legacy POPs in a long-lived Antarctic bird

Seabirds often have high loads of contaminants. These contaminants have endocrine disrupting properties but their relationships with some endocrine mechanisms are still poorly investigated in free-living organisms. This is the case for the stress response which shifts energy investment away from reproduction and redirects it towards survival. In birds, this stress response is achieved through a release of corticosterone and is also accompanied by a decrease in circulating prolactin, an anterior pituitary hormone widely involved in regulating parental cares. We measured blood concentrations of some legacy persistent organic pollutants (POPs) and mercury (Hg) and examined their relationships with the corticosterone and prolactin responses of known-age (9–46years old) incubating snow petrels (Pagodroma nivea) to a standardized capture/handling stress protocol. In this Antarctic seabird, we also investigated whether high contaminant burden correlates with a higher occurrence of egg neglect, a frequently observed behavior in snow petrels. POPs and Hg were unrelated to age. Stress-induced corticosterone concentrations were positively related to POPs in both sexes, and stress-induced prolactin concentrations were negatively related to Hg in males. Egg-neglect behavior was not related to POPs burden, but males with higher Hg concentrations were more likely to neglect their egg. This suggests that in birds, relationships between age and contaminants are complex and that even low to moderate concentrations of POPs and Hg are significantly related to hormonal secretion. In this Antarctic species, exposure to legacy POPs and Hg could make individuals more susceptible to environmental stressors such as ongoing disturbances in Polar Regions.

Recurrence of hyperprolactinemia and continuation of ovarian acyclicity in captive African elephants (Loxodonta africana) treated with cabergoline.

Hyperprolactinemia is associated with reproductive acyclicity in zoo African elephants (Loxodonta africana) and may contribute to the non-self-sustainability of the captive population in North America. It is a common cause of infertility in women and other mammals and can be treated with the dopamine agonist cabergoline. The objectives of this study were to assess prolactin responses to cabergoline treatment in hyperprolactinemic, acyclic African elephants and to determine the subsequent impact on ovarian cyclic activity. Five elephants, diagnosed as hyperprolactinemic (>11 ng/ml prolactin) and acyclic (maintenance of baseline progestagens for at least 1 yr), were treated with 1-2 mg cabergoline orally twice weekly for 16-82 wk. Cabergoline reduced (P < 0.05) serum prolactin concentrations during the treatment period compared to pretreatment levels in four of five elephants (11.5 +/- 3.2 vs. 9.1 +/- 3.4 ng/ml; 20.3 +/- 16.7 vs. 7.9 +/- 9.8 ng/ml; 26.4 +/- 15.0 vs. 6.8 +/- 1.5 ng/ml; 42.2 +/- 22.6 vs. 18.6 +/- 8.9 ng/ml). However, none of the females resumed ovarian cyclicity based on serum progestagen analyses up to 1 yr posttreatment. In addition, within 1 to 6 wk after cessation of oral cabergoline, serum prolactin concentrations returned to concentrations that were as high as or higher than before treatment (P < 0.05). One elephant that exhibited the highest pretreatment prolactin concentration (75.2 +/- 10.5 ng/ml) did not respond to cabergoline and maintained elevated levels throughout the study. Thus, oral cabergoline administration reduced prolactin concentrations in elephants with hyperprolactinemia, but there was no resumption of ovarian cyclicity, and a significant prolactin rebound effect was observed. It is possible that higher doses or longer treatment intervals may be required for cabergoline treatment to result in permanent suppression of prolactin secretion and to mitigate associated ovarian cycle problems.

Extensive investigation of 114 patients with Sheehan's syndrome: a continuing disorder.

Sheehan's syndrome (SS) is a well-known cause of hypopituitarism resulting from postpartum pituitary necrosis. Because of its rarity in Western society, its diagnosis is often overlooked. We aimed to investigate the clinical, laboratory, and radiological aspects of SS in a large number of patients. A retrospective assessment of the medical records of 114 patients with SS was conducted. In addition, sella turcica volumes of 29 healthy women were compared with those of patients by magnetic resonance imaging examinations. The mean period of diagnostic delay was 19.7 years in patients with SS. It was found that 52.6% of patients had nonspecific complaints, 30.7% had complaints related to adrenal insufficiency, and 9.6% had complaints related to hypogonadism when diagnosed. At the time of diagnosis, 55.3% of the patients had panhypopituitarism, while 44.7% had partial hypopituitarism. The number of deficient hormones was found to be increased over the years. None of the patients whose basal prolactin was below 4.0 ng/ml had adequate prolactin responses to TRH test, while all patients whose basal prolactin was above 7.8 ng/ml had adequate responses. Mean sella volume was found to be significantly lower in the SS group (340.5±214 mm(3)) than that in the healthy group (602.5±192 mm(3)). SS is a common cause of hypopituitarism in underdeveloped and developing countries. The main reasons for diagnostic delay seem to be the high frequency of patients with nonspecific complaints and neglect of SS. In addition, the TRH stimulation test was found to have a high sensitivity and specificity to recognize PRL deficiency. Furthermore, small sella size may have an important contributing role in the etiopathogenesis of SS.

Opioid modulation of prolactin secretion induced by stress during late pregnancy. Role of ovarian steroids

BackgroundThe opioid system modulates prolactin release during late pregnancy. Its role and the participation of ovarian hormones in this modulation are explored in ether stress-induced prolactin release. Methods/ResultsEstrous, 3-day and 19-day pregnant rats were used. We administered the antagonist mifepristone (Mp) and tamoxifen to evaluate progesterone and estradiol action in naloxone (NAL, opioid antagonist) or saline treated rats. Ether stress had no effect on serum prolactin levels in controls but increased prolactin release in NAL-treated rats. Prolactin response to stress in NAL-treated rats was blocked by l-DOPA administration. Mp treatment on day 18 of pregnancy increased prolactin levels after stress without alterations by NAL. Tamoxifen on days 14 and 15 of pregnancy completely blocked Mp and NAL effects on prolactin release at late pregnancy. In contrast, stress significantly increased prolactin levels in estrous rats and pretreatment with NAL prevented this. On day 3 of pregnancy, at 6.00 p.m., stress and NAL treatment inhibited prolactin levels in saline-treated rat. No effect of stress or NAL administration was detected on day 3 of pregnancy at 9.00 a.m. icv administration of specific opioids antagonist, B-Funaltrexamine but not Nor-Binaltorphimine or Naltrindole, caused a significant increase in stress-induced prolactin release. ConclusionsOpioid system suppression of prolactin stress response during late pregnancy was observed only after progesterone withdrawal, involving a different opioid mechanism from its well-established stimulatory role. This mechanism acts through a mu opioid receptor and requires estrogen participation. The opioid system and progesterone may modulate stress-induced prolactin release, probably involving a putative prolactin-releasing factor.

Effects of Heat Acclimation on Time Perception

Physical and mental performance is impaired during prolonged exercise in hot environments (Gonzalez-Alonso et al., 1999) compared to thermoneutral conditions. These effects are related to changes in body temperature and alterations in the central nervous system functioning (CNS; Nybo & Nielsen, 2001). Repeated exposure to exercise-related heat stress results in physiological adaptations that, in turn, lead to performance improvements (Burk et al., 2012; Wendt et al., 2007). Exploring temporal processing with temperature manipulations suggests the existence of a temperature sensitive time mechanism that is mediated through the level of arousal (Wearden & Penton-Voak, 1995). However, we recently demonstrated that in addition to physiological factors like core temperature, psychological response to heat stress should be considered as well (Tamm et al., 2013).Healthy young male participants took part in two slightly different acclimation programs (i.e., daily moderate exercise at similar ambient temperature). The first group (N=20) followed a 10-day program with gradual increase in exercise intensity (first half of the program at 55% of individual VO2max and second half at 60% of individual VO2max) with two 50-min exercise periods on a treadmill, separated with a 10-min rest period. The second group (N=20) participated in an 8-day acclimation program where they exercised at varying intensity level to keep the core temperature at a fixed level of 38.5-39°C. The exercise trial consisted of three 30-min periods of exercise separated with two 5-min rest periods. Before (H1) and after (H2) the acclimation programs, both groups performed acute exercise trial until exhaustion at 42°C with the humidity level at 18%. In the control condition, participants exercised in a thermoneutral environment (22°C), duration equal to H1 trial. Several state indicators like core temperature (T) and heart rate (HR), ratings of perceived fatigue and exertion (CR-10 & RPE, respectively; Borg, 1998), critical flicker frequency (CFF) were obtained for estimating both physiological and psychological perspectives on status change. In addition, participants performed cognitive testing measuring performance in short-term and working memory tasks under stressful conditions. Blood samples for estimating changes in hormone measures were included. Previous results indicate the response of blood prolactin (PRL) to exercise in the heat is related to endurance capacity and the rate of increase of PRL concentration is reduced after heat acclimation (Burk et al., 2012). Acclimation effects on cognitive performance, including time perception, are seldom if ever explored. The current study investigates time production during acute exercise in the hot environment before and after heat acclimation program. More precisely, we are interested in the physiological and psychological factors that contribute to the temporal performance under stressful conditions and what are the characteristics of adaptation to such conditions.A time production task was administered before, after 10 and 60min of exercise, and after ending the trial. Heart rate, temperature, and subjective state measures were obtained during the exercise with a 10-min interval. Blood samples were collected before, during (at 60min) and after the exercise trial. Linear function was used for analyzing the relationship between subjective time and real time in a time production task. If regression coefficient is sufficiently close (a1=1) then produced time intervals are identical to time intervals indicated by the task. The results showed that for both groups, significant temporal compression occurred (a1<1) after 60min of exercise, relative to pre-trial coefficients. However, this effect was absent when exercising in the hot environment after heat acclimation, irrespective of the acclimation program. Additionally, adaptations in physiological and psychological measures were present. In conclusion, heat acclimation slows down the increase in respective measures and, thus, performance improvements are observed. Further, when the relationship between time production task and other experimental measures was explored, the hormonal measures were important in describing the effects in temporal performance. The results are explained and specified within the internal clock model in terms of arousal effects on the pacemaker-accumulator functioning.

Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells

Resveratrol (RE), a phytoestrogen, has antiestrogenic properties. Estrogen plays a key role in the development and progression of pituitary prolactinoma. Moreover, RE is a potent cancer chemopreventive agent that inhibits the initiation, promotion and progression of carcinogenesis. The present study investigated the antitumor effects of RE on GH3 pituitary tumor cells. A concentration- and treatment duration-dependent biphasic effect of RE on the proliferation of the GH3 cells was demonstrated. After three days of treatment, RE stimulated proliferation at low concentrations and inhibited proliferation at high concentrations. However, when the treatment duration was reduced to 6 h, RE inhibited proliferation in a concentration-dependent manner. In addition, RE induced apoptosis with the activation of caspase-3 and -8, and decreased the percentage of prolactin (PRL)-immunopositive GH3 cells. Furthermore, RE suppressed expression of the PRL gene and inhibited the cell proliferation and PRL synthesis induced by 17β-estradiol (E2). In GH3 cells, the proliferation response exhibited higher sensitivity to E2 compared with the PRL response; by contrast, the PRL response was more sensitive to RE than the proliferation response was. These results indicate that RE, an antiestrogenic compound, exerts its antitumor effect on GH3 cells through the suppression of GH3 cell growth and through the inhibition of PRL synthesis. The RE-induced cell apoptosis was shown to be caspase-dependent. Therefore, the present study provides support for the use of RE in the chemoprevention and chemotherapy of pituitary prolactinoma.

The Effect of Prolactin in Response to Academic Stress during Examination Condition in Healthy Male and Female University Students

The effect of Prolactin in response to academic stress was studied in forty healthy male and female University students during their final year seminar presentation examination. The data collected are some Anthropometric parameters, Blood pressure (diastolic and systolic) and prolactin level. The arterial blood pressure was measured by auscultatory method using stethoscope and sphygmomanometer. Serum prolactin level in blood sample collected from each subject was analyzed using prolactin ELISA kit. The serum prolactin level in students under examination condition when compared to students not under examination increased significantly (P<0.05). The blood pressure also increased with a significant statistical value (P<0.05) when the test group was compared to the control group. It can therefore be inferred that Prolactin level increases in academic stress in both male and female may be a useful neuro-endocrine link to stress.

Long-term Treatment of Insulin-insensitive Mares with Cabergoline: Effects on Prolactin and Melanocyte Stimulating Hormone Responses to Sulpiride and on Indices of Insulin Sensitivity

The main experiment assessed whether the inhibitory effects of the dopamine agonist, cabergoline, on prolactin and α-melanocyte stimulating hormone (MSH) concentrations would persist throughout a longer-term administration (65 days). The possible effect of cabergoline on insulin sensitivity was also studied. Ten mares known to be insulin insensitive were allotted to two groups (treated vs. control). An insulin challenge, a glucose tolerance test, and a sulpiride challenge were administered before treatment. On day 0, treated mares (n = 5) received an injection of 5 mg cabergoline in slow-release vehicle; control mares (n = 5) received an equivalent vehicle injection. Injections were repeated every 10 days for a total of seven injections. Sulpiride challenges were done 1 day before each cabergoline treatment to assess possible refractoriness to the treatment. Behavior and hair coat density were also monitored. Plasma prolactin was suppressed (P < .01) to undetectable levels in mares receiving cabergoline; control mares had robust prolactin responses to each sulpiride injection. There was no indication of refractoriness to cabergoline over time. Plasma MSH concentrations after sulpiride were also suppressed (P < .05) by cabergoline. After treatment, neither the glucose response to insulin nor the insulin response to glucose differed (P > .1) between groups. No behavioral changes were noted because of treatment. Weight of hair samples indicated that cabergoline perturbed (P < .05) winter coat growth. It is concluded that 5 mg of cabergoline in slow-release vehicle administered every 10 days is an effective way of delivering dopaminergic activity to mares that results in no noticeable detrimental effects and no refractoriness to the drug.

Adipose Tissue Macrophages (ATM) of obese patients are releasing increased levels of prolactin during an inflammatory challenge: A role for prolactin in diabesity?

BackgroundObesity, characterized by low grade inflammation, induces adipose tissue macrophage (ATM) infiltration in white adipose tissue (AT) in both humans and rodents, thus contributing to insulin resistance. Previous studies have shown altered prolactin secretion in obesity, however, studies linking ATM infiltration and prolactin (PRL) secretion to the pathogenesis of the metabolic syndrome, obesity and diabetes are lacking. Methods/ResultsIn vivo, qPCR and Western blot analysis demonstrated that prolactin expression was increased in AT of obese rats and also in human AT from obese, obese pre-diabetic and obese diabetic compared to lean counterparts. Immunohistochemistry of obese rat and human AT sections demonstrated a specific expression of prolactin in macrophages. In vitro, we demonstrated that hyperglycemia and inflammation stimulated macrophages (human THP-1 cell line and sorted rat ATM) to express PRL, when challenged with different glucose concentrations with or without IL1β. In in vivo and in vitro experiments, we assessed the expression of Pit-1 (PRL-specific transcription factor) and found that its expression was parallel to PRL expression. ConclusionsIn this study, we show that rodent and human macrophages synthesize prolactin in response to inflammation and high glucose concentrations. General significanceOur data shed new light on the potential role of macrophages in the physiopathology of diabesity via the PRL expression and on its expression mechanism and regulation.

Recent advances in the use of an estradiol-dopamine antagonist protocol to induce ovulation in seasonally anovulatory mares

The January 1 birthday imposed by major breed registries is in conflict with the natural breeding season of the mare. Without intervention, breeders are denied the documented advantages in price and performance of foals born earlier in the year [1]. Dopamine antagonists have been used to induce early ovulation in anovulatory mares [2,3,4,5]. Kelley and associates [6] were the first to report the enhancement of prolactin secretion and superior advancement of first ovulation by pretreatment with estradiol benzoate prior to the administration of dopamine antagonist. The protocol described by Kelley et al. (6) was streamlined by Thompson et al. [7], who found that a single injection of estradiol cypionate (ECP) gave consistent prolactin and luteinizing hormone responses equivalent to those observed by Kelley et al. [6]. Subsequently, it was shown that a single injection of ECP followed by a single injection of the dopamine antagonist domperidone advanced first ovulation in anovulatorymares inwinter [8], although with a lower success rate than the earlier, more complicated protocols. The experiments described herein were conducted to assess potential improvements in the ECP-dopamine antagonist protocol for inducing ovulation in seasonally anovulatory mares.

Compromise of Endogenous Neuropeptide W Production Abrogates the Dipsogenic and Pressor Effects of Angiotensin II in Adult Male Rats

Neuropeptide W (NPW), an endogenous ligand for the G-protein coupled receptor GPR7, is produced in neurones in the rat hypothalamus and brain stem known to be important in the control of food intake and the neuroendocrine response to stress. In previous studies, central administration of NPW during the light phase increased food and water intake and elevated prolactin and corticosterone levels in conscious, unrestrained male rats. In the present study, central administration of small-interfering RNA (siRNA) reduced NPW levels in the hypothalamus and resulted in a failure of angiotensin II to stimulate water drinking or increase mean arterial pressure. In addition, siRNA-treated animals failed to mount a significant prolactin response to immobilisation stress, at the same time as maintaining a normal corticosterone response. These results suggest that endogenous NPW may be a physiologically relevant, downstream mediator of the central actions of angiotensin II to stimulate thirst and increase arterial pressure. In addition, NPW-producing neurones appear to participate in the hypothalamic mechanisms controlling prolactin (but not corticosterone) secretion.

Prolactin and fMRI response to SKF38393 in the baboon.

Background. This study’s goal was to provide dose–response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose–response curves.Methods. We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m. ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D1-like agonists SKF82958 and SKF38393 or the D2-like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928–9.28 mg/kg, N = 5 animals) or pramipexole (0.00928–0.2 mg/kg, N = 1) was given i.v. during a 40-min blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 min after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED50 (estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain.Results. Prolactin rose 2.4- to 12-fold with anesthesia alone, peaking around 50–90 min after ketamine administration and gradually tapering off but still remaining higher than baseline on isoflurane 3–5 h after ketamine. Baseline prolactin level increased with age. SKF82958 0.1 mg/kg i.v. produced no noticeable change in plasma prolactin concentration. SKF38393 produced a substantial increase in prolactin release that peaked at around 20–30 min and declined to pre-drug levels in about an hour. Pramipexole quickly reduced prolactin levels below baseline, reaching a nadir 2–3 h after infusion. SKF38393 produced clear, dose-responsive BOLD signal changes, and across the four regions, ED50 was estimated at 2.6–8.1 mg/kg.Conclusions. In the baboon, the dopamine D1 receptor agonist SKF38393 produces clear plasma prolactin and phMRI dose–response curves. Variability in age and a modest sample size limit the precision of the conclusions.

Prolactin response to buspirone is not impaired in drug-naïve first episode patients with major depressive disorder

BackgroundAn altered postsynaptic 5-HT1A receptor function along with hypercortisolemia has been associated with major depressive disorder (MDD). However, several methodological considerations related to data interpretation arise when subjects previously exposed to psychotropic medication are included in the study population. To address those issues we designed a study in a well defined cohort of first-episode, treatment-naïve MDD patients. MethodsThis cross-sectional case–control pharmacologic challenge study was designed to investigate the prolactin (PRL) response to buspirone in 21 non-late-life adult, treatment-naïve MDD patients with the first affective episode and in 20 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20. ResultsNo significant difference in PRL response to buspirone between first-episode, treatment-naïve patients with MDD and controls, was observed. The correlation between basal cortisol levels and PRL response was not observed in MDD group while significant negative correlation was found in healthy controls. The significantly higher PRL response to buspirone was observed in melancholic patients as compared to non-melancholic subjects. LimitationsThe current study is limited by its cross-sectional design, small sample size, factors related to neuroendocrine challenge methodology, and no placebo control. ConclusionThese results indicate no consistent changes in the hormonal response to the 5-HT1A agonist buspirone in major depression. Taken into account the interpretation of the buspirone test the present study does not support the hypothesis of an altered functional activity with down-regulation of the postsynaptic 5-HT1A receptor and/or in the postsynaptic receptor signal transduction in the hypothalamus in the pathogenesis of MDD.

Cannabinoid-induced upregulation of serotonin 2A receptors in the hypothalamic paraventricular nucleus and anxiety-like behaviors in rats

Recent behavioral reports suggest that repeated exposure to cannabis and synthetic cannabinoid agonists is linked with mental disorders associated with dysfunction of serotonin 2A (5-HT2A) receptor neurotransmission such as anxiety and depression. Here, we studied the effect of a nonselective cannabinoid agonist, CP55940, on the activity of 5-HT2A receptors in hypothalamic paraventricular nucleus (PVN). We detected that repeated exposure to CP55940 enhanced the prolactin and corticosterone neuroendocrine responses mediated by 5-HT2A receptors and increased the membrane-associated levels of 5-HT2A receptors in PVN. Importantly, we also detected increased anxiety-like behaviors in CP55940 treated rats compared to controls. The data presented here suggest that the mechanisms mediating the cannabinoid-induced upregulation of 5-HT2A receptors would be brain-region specific, as we were unable to detect a CP55940-induced upregulation of 5-HT2A mRNA. Our results might provide insight into the molecular mechanism by which repeated exposure to cannabinoids could be associated with the pathophysiology of neuropsychiatric disorders.

Long-term treatment of insulin insensitive mares with cabergoline: Effects on insulin sensitivity, insulin response to glucose infusion, and prolactin response to sulpiride

[1] Muller CE, Von Rosen D, Uden P. Effect of Forage conservation method on microbial flora and fermentation pattern in forage and in equine colon and faeces. Livestock Science 2008;Volume 119:116-28. [2] Muhonen S, Julliand V, Lindbeg JE, Bertilsson J, Jansson A. Effects on the equine colon ecosystem of grass silage and haylage diets after an abrupt change from hay. Journal of Animal Science 2009;Volume 87: 2291-8.

Small-dose sulpiride injections in horses: Repeatability of prolactin responses and use for assessment of dopaminergic suppressive activity by pergolide and cabergoline formulations

s / Journal of Equine Veterinary Science 33 (2013) 321-399 370 gradient would in theory increase the concentration of higher quality sperm in the insemination dose. With stallions whose semen parameters are less than optimal, such a separation would be desirable for eliminating the abnormal sperm in the insemination dose and from potentially competing with normal sperm within the mare’s reproductive tract. The process for preparing for the centrifugation is costly from the standpoint of time but the result is a more viable insemination dose. On a commercial breeding operation during the summer of 2012, this process was employed to attempt to improve pregnancy rates in mares bred to a stallionwith documented subfertile semen parameters. A commercially-available equine sperm purification protocol, EquiPure, was used as the treatment in 92 the stallion’s ejaculate. One hundred ninety seven mares were inseminated with either treated (EquiPure) or nontreated semen. Thirty-two of the 63 mares bred with the treated insemination doses were pregnant (51%). Of the 134 mares bred with the non-treated semen, 75 were determined to be in foal (56%). There was no difference in pregnancy rates between themares inseminatedwith treated or untreated semen. For the 67 mares bred on the farm, 15 became pregnant when the ejaculates had been treated with EquiPure and 23 were pregnant when bred with nontreated semen resulting in 68% vs 51% pregnant, respectively. There were 130 mares bred with cooled transported semen; only 17 bred with EquiPure treated semen were pregnant (41%) vs 52with non-treated shipped semen 58%). For this stallion, the treatment with EquiPure did not significantly improve the pregnancy rate in the mares. Therefore, it was determined, for this stallion, that the process would not be employed in future breeding. Unfortunately, because of the many variables of breeding in the commercial setting, the positive results observed in a controlled laboratory setting did not carry over to the

Restraint effects on stress-related hormones and blood natural killer cell cytotoxicity in pigs with a mutated ryanodine receptor

A mutation in the ryanodine receptor gene (RYR1) of the calcium release channel is responsible for increased stress susceptibility in pigs. In the present study, the relation of a mutation in RYR1 with the neuroendocrine (stress-related hormone) response and the immune defense represented by natural killer cell cytotoxicity (NKCC) during a 4-h restraint and recovery phase in 60 male pigs was investigated. Blood samples were collected from pigs previously divided into RYR1 genotypes (nn, Nn, NN), based on PCR amplification and restriction analyses. The blood samples collected during the restraint and recovery phases of the experiment were used to determine NKCC (51Cr-release assay), large granular lymphocyte number (hematologic method), and plasma concentrations of prolactin (PRL), GH, ACTH, and cortisol (COR) (by specific RIA). The greatest degree of NKCC response (P < 0.05) to restraint stress relative to controls was observed for the stress-susceptible homozygote group (nn). Measures of stress-related hormones were positively correlated with NKCC during the entire experimental period (P < 0.001 for all investigated hormones) in the nn group. Immunostimulatory effects in the early (0–60 min) phase of restraint were associated with increased hormone responses, especially PRL and GH. In the late (180–240 min) phase of stress and the recovery phase (480 min), a decrease in immune response was accompanied by an elevated COR response in all RYR1 genotypes. Moreover, divergent responses of both PRL (greatest in nn, P < 0.001) and GH (greatest in NN, P < 0.001) to the 4-h restraint were observed. Our results suggest that stress-susceptible RYR1-mutated homozygotes develop a greater level of immune defense, including cytotoxic activity of NK cells, and accompanied by more pronounced stress-induced changes in neuroendocrine response than stress-resistant heterozygous (Nn) and homozygous (NN) pigs.