024 Quiescent Wakefulness: Characterising the Impact of Oxytocin on Sleep-Wake Behaviour in Male and Female Rats

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A11
Author(s):  
Joel Raymond ◽  
Nicholas Everett ◽  
Anand Gururajan ◽  
Michael Bowen
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Conscious State ◽  
Positive Control ◽  
Female Rats ◽  
Male And Female ◽  
Routes Of Administration ◽  
Male And Female Rats ◽  
Competing Hypotheses ◽  
The Impact

Abstract Introduction Oxytocin is a versatile hypothalamic neuropeptide involved in diverse neurobehavioural processes. Since oxytocin can elicit anxiolytic and serenic effects, one could hypothesise that oxytocin should prime the brain for sleep and promote hypnogenesis. However, based on the social salience hypothesis—that oxytocin promotes prosocial behaviour and directs attention toward social stimuli—one could also posit that oxytocin should promote wakefulness. At present, little research has comprehensively characterised the effect of oxytocin on sleep-wake behaviour and no explanation to reconcile these two seemingly competing hypotheses has been proposed. Methods This study investigated the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via the intraperitoneal (IP; 0.1, 0.3 and 1 mg/kg) and intranasal (IN; 0.06, 1, 3 mg/kg) routes. Caffeine (IP and IN; 10 mg/kg) was also administered as a wake-promoting positive control. Additionally, pre-treatment with the oxytocin receptor (OTR) antagonist L-368,899 (IP; 5 mg/kg) and vasopressin 1a receptor (V1aR) antagonist SR49059 (IP; 1 mg/kg) followed by oxytocin (IP; 1 mg/kg) was conducted to determine which receptor(s) mediated sleep-wake effects of oxytocin. Results In both male and female rats, IP oxytocin produced dose-dependent effects on sleep-wake behaviour. Specifically, oxytocin initially promoted quiescent wakefulness (a restful but conscious state) at the cost of reducing both active wakefulness and sleep. Throughout the 1.5-hour period post-administration, oxytocin delayed REM sleep onset and reduced the proportion of both NREM and REM sleep. Conversely, IN oxytocin did not significantly alter any sleep-wake parameters at any dose tested. Caffeine demonstrated wake-promoting effects under both the IP and IN routes of administration. The involvement of OTR and V1aR binding in oxytocin-induced effects on sleep-wake outcomes will be discussed. Conclusion These findings appear to reconcile the two competing hypotheses: in rats, IP oxytocin appears to promote a state of quiescent wakefulness—one of calm and rest, but also of conscious responsivity to environmental stimuli. IN oxytocin demonstrated little to no effect on sleep-wake behaviour, which is a crucial finding given the escalating use of IN oxytocin as a therapeutic for conditions with comorbid disordered sleep. Support (if any) None.

scholarly journals NONCLINICAL STUDY OF THE TOXICITY OF A NEW ANTICANCER DRUG ОRMUSTIN ON SMALL LABORATORY ANIMALS

2015 ◽  
Vol 14 (4) ◽  
pp. 65-72 ◽  
Author(s):  
V. A. Chaley ◽  
O. I. Konyaeva ◽  
N. P. Ermakova ◽  
A. A. Nikolina ◽  
V. M. Bukhman ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Intravenous Administration ◽  
Female Rats ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Male And Female ◽  
Male And Female Rats ◽  
The Impact ◽  
Hybrid Mice ◽  
Nonclinical Study

The paper presents the results of the study of «acute» toxicity and some results of the study of «subchronic» toxicity of Ormustin, a new anticancer drug belonging to nitrosourea class, in small laboratory animals. In the experiments the laboratory animals - hybrid mice (C57Bl/6J×DBA/2)F1 male and female and outbred male and female rats have been used. On the results of study has been obtained the calculated toxic doses of Ormustin at intravenous administration of the drug in mice and rats; has been given the preliminary assessment of the impact of Ormustin on organs and systems of rats at multiple intravenous administration.

scholarly journals Sex Differences in the Renal Vascular Responses of AT1 and Mas Receptors in Two-Kidney-One-Clip Hypertension

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zahra Pezeshki ◽  
Mehdi Nematbakhsh
Keyword(s):  
Sex Differences ◽  
Female Rats ◽  
Receptor Interaction ◽  
Ang Ii ◽  
Male And Female ◽  
Vascular Responses ◽  
Mas Receptor ◽  
Male And Female Rats ◽  
Renal Vascular ◽  
The Impact

Background. The prevalence and severity of hypertension, as well as the activity of the systemic and local renin angiotensin systems (RASs), are gender related, with more symptoms in males than in females. However, the underlying mechanisms are not well understood. In this study, we investigated sex differences in renal vascular responses to angiotensin II (Ang II) administration with and without Ang II type 1 and Mas receptor (AT1R and MasR) antagonists (losartan and A779) in the 2K1C rat model of renovascular hypertension. Methods. Male and female 2K1C rats were divided into 8 experimental groups (4 of each sex) treated with vehicle, losartan, A779, or A779+losartan. Responses of mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) to Ang II were determined. Results. In both sexes, the basal MAP, RBF, and RVR were not significantly different between the four groups during the control period. The Ang II administration decreased RBF and increased RVR in a dose-related manner in both sexes pretreated with vehicle or A779 ( P dose < 0.0001 ), but in vehicle pretreated groups, RBF and RVR responses were different between male and female rats ( P group < 0.05 ). AT1R blockade increased RBF and decreased RVR responses to Ang II, and no difference between the sexes was detected. Coblockades of AT1R and MasR receptors increased RBF response to Ang II significantly in males alone but not in females ( P group = 0.04 ). Conclusion. The impact of Ang II on RBF and RVR responses seems to be gender related with a greater effect on males, and this sex difference abolishes by Mas receptor blockade. However, the paradoxical role of dual losartan and A779 may provide the different receptor interaction in RAS between male and female rats.

scholarly journals High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 89
Author(s):  
Soniya Xavier ◽  
Jasmine Gili ◽  
Peter McGowan ◽  
Simin Younesi ◽  
Paul F. A. Wright ◽  
...  
Keyword(s):  
Maternal Diet ◽  
Female Offspring ◽  
Female Rats ◽  
Omega 3 ◽  
Male And Female ◽  
Offspring Development ◽  
Metabolic Outcomes ◽  
Male And Female Rats ◽  
The Impact

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.

Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei

2005 ◽  
Vol 289 (2) ◽  
pp. R353-R358 ◽  
Author(s):  
Paul J. Currie ◽  
Aaisha Mirza ◽  
Rebecca Fuld ◽  
Diana Park ◽  
Joseph R. Vasselli
Keyword(s):  
Food Intake ◽  
Substrate Utilization ◽  
Open Circuit ◽  
Female Rats ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Male And Female ◽  
Energy Substrate ◽  
Male And Female Rats ◽  
The Impact

Ghrelin is a 28-amino acid acylated peptide and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The GHS-R is expressed in hypothalamic nuclei, including the arcuate nucleus (Arc) where it is colocalized with neuropeptide Y (NPY) neurons. In the present study, we examined the effects of ghrelin on feeding and energy substrate utilization (respiratory quotient; RQ) following direct injections into either the arcuate or the paraventricular nucleus (PVN) of the hypothalamus. Ghrelin was administered at the beginning of the dark cycle at doses of 15–60 pmol to male and female rats. In feeding studies, food intake was measured 2 and 4 h postinjection. Separate groups of rats were injected with ghrelin, and the RQ (V̇co2/V̇o2) was measured using an open circuit calorimeter over a 4-h period. Both Arc and PVN injections of ghrelin increased food intake in male and female rats. Ghrelin also increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. Because these effects are similar to those observed after PVN injection of NPY, we then assessed the impact of coinjecting ghrelin with NPY into the PVN. When rats were pretreated with very low doses of ghrelin (2.5–10 pmol), NPY's (50 pmol) effects on eating and RQ were potentiated. Overall, these data are in agreement with evidence suggesting that ghrelin functions as a gut-brain endocrine hormone implicated in the regulation of food intake and energy metabolism. Our findings are also consistent with a possible interactive role of hypothalamic ghrelin and NPY systems.

scholarly journals Gender Difference Response of Male and Female Immunodeficiency Rats Treated with Tissue-specific Biomolecules

2019 ◽  
Vol 20 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Liliya V. Fedulova ◽  
Alexandr A. Basov ◽  
Ekaterina R. Vasilevskaya ◽  
Stepan S. Dzhimak
Keyword(s):  
Hematological Parameters ◽  
Cellular Level ◽  
Female Rats ◽  
Male Rats ◽  
Mesenteric Lymph Nodes ◽  
Bile Formation ◽  
Male And Female ◽  
Tissue Specific ◽  
Male And Female Rats ◽  
The Impact

Background:The modern immunology is targeted to the detailed study of various immunopathological conditions at the molecular and cellular level, development of new methods for the prevention, diagnostics and treatment of contagious and non-contagious diseases of humans and animals.Methods:In the present work we took the rats with model of cyclophosphamide-induced immunodeficiency and studied the features of gender impact of the complex extract of immunocompetent organs (thymus, spleen and mesenteric lymph nodes) Sus scrofa and its separate fraction with molecular weight less than 30 kDa administered to male and female rats.Results:The impact of gender differences and tissue-specific biomolecules (30 kDa fraction) on hematological parameters (leukocytes, erythrocytes, platelets), functional activity of immune system (IL-2, IL-4, IL-6, complement system, IgG, IgM), biochemical parameters of hepatocytes functioning (activity of ALP and LDG), carbohydrate metabolism (glucose) and lipid metabolism (triglycerides).Conclusion:Decrease of ALP activity is caused by inhibition of bile formation in a liver after introduction of cytostatic agent, and in contrast to complex extract, the administration of fraction 30 kDa allows improving bile production in male rats.

scholarly journals THC modifies the impact of heroin delivered by vapor inhalation in rats

2021 ◽  
Author(s):  
Arnold Gutierrez ◽  
Jacques D. Nguyen ◽  
Kevin M. Creehan ◽  
Mehrak Javadi-Paydar ◽  
Yanabel Grant ◽  
...  
Keyword(s):  
Positive Outcome ◽  
Female Rats ◽  
Physiological Effects ◽  
Additive Effects ◽  
Sprague Dawley ◽  
Independent Manner ◽  
Male And Female ◽  
Thermal Nociception ◽  
Male And Female Rats ◽  
The Impact

AbstractOpioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms. This study was conducted to determine if heroin and Δ9-tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature and spontaneous locomotor activity when inhaled or injected.Groups of male and female rats implanted with radiotelemetry transmitters were exposed to vapor for assessment of effects on temperature and activity. Heroin (50 mg/mL in the propylene glycol; PG) inhalation increased temperature and activity whereas THC (50 mg/mL) inhalation decreased temperature and activity. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of Heroin and THC by either inhalation or injection produced additive effects on thermal nociception assessed with a warm water tail-withdrawal assay in male and female Sprague-Dawley and Wistar rats.The conclusion of this study is that additive effects of THC with heroin on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects.

scholarly journals Advanced age attenuates the antihyperalgesic effect of morphine and decreases μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray in male and female rats

2020 ◽  
Author(s):  
Evan F. Fullerton ◽  
Myurajan Rubaharan ◽  
Mary C. Karom ◽  
Richard I. Hanberry ◽  
Anne Z. Murphy
Keyword(s):  
Opioid Receptor ◽  
Receptor Expression ◽  
Female Rats ◽  
Advanced Age ◽  
Adult Males ◽  
Male And Female ◽  
Male And Female Rats ◽  
Age Related ◽  
Μ Opioid Receptor ◽  
The Impact

AbstractThe present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on μ-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund’s adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population.

Differential orderliness of the GH release process in castrate male and female rats

1998 ◽  
Vol 274 (2) ◽  
pp. R437-R444 ◽  
Author(s):  
Evelien Gevers ◽  
Steve M. Pincus ◽  
Iain C. A. F. Robinson ◽  
Johannes D. Veldhuis
Keyword(s):  
Gnrh Agonist ◽  
Rank Order ◽  
Female Rats ◽  
Sex Steroid ◽  
Intact Male ◽  
Castrate Male ◽  
Male And Female ◽  
Releasing Hormone ◽  
Male And Female Rats ◽  
The Impact

Male- and female-specific modes of episodic growth hormone (GH) release are presumptively imposed by sex steroid hormones, and, although typically evident visually, are vividly distinguished quantitatively via a regularity statistic, approximate entropy (ApEn), in both the rat and human. GH secretory patterns may determine GH-stimulated growth and specific hepatic and muscle gene expression in the rat. Consequently, it is important to discern mechanisms that underlie their regulation. Here we have examined the impact of prepubertal gonadal suppression (at 4 wk of age) via surgical or pharmacological [gonadotropin-releasing hormone (GnRH) agonist] intervention on the regularity (ApEn) of GH release in male and female rats (at 10–11 wk of age) sampled at 10-min intervals for 10 h ( n = 60 points) during a lights-out (dark) period. We observed a graded hierarchy of mean disorderliness of GH release that was quantifiable by ApEn measures, with maximal to minimal disorderliness in the following rank order: intact female, GnRH agonist-treated female, ovariectomized female, orchidectomized male, GnRH agonist-treated male, and intact male. These observations suggest a continuum of sex steroid actions on the regularity of GH secretion and, by inference, on the interplay among GH-releasing hormone, somatostatin, and GH/insulin-like growth factor I negative feedback.

scholarly journals Ames mutagenicity, structural alerts of carcinogenicity, Hansch QSAR parameters (ClogP, CMR, MgVol), tumor site concordance/multiplicity, and tumorigenicity rank in NTP 2-year rodent studies

2018 ◽  
Vol 2 ◽  
pp. 239784731875932
Author(s):  
Carr J Smith ◽  
Thomas A Perfetti ◽  
Gene M Ko ◽  
Rajni Garg
Keyword(s):  
Quantitative Structure Activity Relationship ◽  
Female Rats ◽  
Molecular Volume ◽  
Tumor Site ◽  
Male And Female ◽  
Routes Of Administration ◽  
Male And Female Rats ◽  
Rank Score ◽  
Structural Alerts ◽  
Qsar Parameters

Since its inception in 1976, the National Toxicology Program (NTP) has conducted 594 2-year studies on rats and mice by a number of routes of administration including inhalation, feed, drinking water, dermal, and intraperitoneal injection. Of these studies, the results on 470 chemicals were of adequate technical quality to be incorporated into final technical reports. In this study, the 470 chemicals were categorized from 1 to 48 by the level of “clear” neoplastic evidence in male and female rats, and in male and female mice, and given an ordinal rank from 1 to 135 following additional considerations regarding tumor site concordance and tumor multiplicity. The resultant tumorigenicity category score and ordinal rank score were examined for associations with results in the Ames Salmonella mutagenicity assay; presence or absence of structural alerts of carcinogenicity; and three Hansch Quantitative Structure-Activity Relationship (QSAR) parameters, namely, calculated base 10 logarithm of the octanol–water partition coefficient (ClogP), calculated molar refractivity (CMR), and McGowan molecular volume (MgVol). Smaller molecular volumes were found to be associated with higher levels of tumorigenicity. Whereas lower rather than higher levels of lipophilicity were found to be associated with higher levels of tumorigenicity. Positive Ames test results were positively correlated with overall tumorigenicity and with possession of structural alerts. Since larger organic molecules have more chemical reaction centers, it was not surprising that higher ClogP values were positively correlated with the number of structural alerts. The results from this study demonstrate the ability to devise rational rules for relative tumorigenicity that correlate, in biologically plausible ways, with known parameters of toxicity.

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