scholarly journals Sex- and Subtype-Specific Adaptations in Excitatory Signaling Onto Deep-Layer Prelimbic Cortical Pyramidal Neurons After Chronic Alcohol Exposure

2021 ◽  
Author(s):  
Benjamin A. Hughes ◽  
Todd K. O’Buckley ◽  
Giorgia Boero ◽  
Melissa A. Herman ◽  
A. Leslie Morrow
Keyword(s):  
Working Memory ◽  
Deep Layer ◽  
Cell Activity ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Gabaergic Neurotransmission ◽  
Male And Female Rats

ABSTRACTLong-term alcohol use results in behavioral deficits including impaired working memory, elevated anxiety, and blunted inhibitory control that are associated with prefrontal cortical (PFC) dysfunction. Preclinical observations demonstrate multiple impairments in GABAergic neurotransmission onto deep-layer principal cells (PCs) in prelimbic cortex that suggest dependence-related cortical dysfunction is the product of elevated excitability in these cells. Despite accumulating evidence showing alcohol-induced changes in interneuron signaling onto PCs differ between sexes, there is limited data explicitly evaluating sex-specific ethanol effects on excitatory signaling onto deep-layer PCs that may further contribute to deficits in PFC-dependent behaviors. To address this, we conducted electrophysiological and behavioral tests in both male and female Sprague-Dawley rats to evaluate the effects of chronic ethanol exposure. Among our observations, we report a marked enhancement in glutamatergic signaling onto deep-layer PCs in male, but not female, rats after alcohol exposure. This phenomenon was furthermore specific to a sub-class of PC, sub-cortically projecting Type-A cells, and coincided with enhanced anxiety-like behavior, but no observable deficit in working memory. In contrast, female rats displayed an alcohol-induced facilitation in working memory performance with no change in expression of anxiety-like behavior. Together, these results suggest fundamental differences in alcohol effects on cell activity, cortical sub-circuits, and PFC-dependent behaviors across male and female rats.

scholarly journals Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

2018 ◽  
Vol 7 (5) ◽  
pp. 412-418
Author(s):  
Mohd Urooj ◽  
◽  
Mohammad Ahmed Khan ◽  
G. Thejaswini ◽  
Munawwar Husain Kazmi ◽  
...  
Keyword(s):  
Body Weight ◽  
Feed Intake ◽  
Clinical Signs ◽  
Female Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Male And Female ◽  
Salix Caprea ◽  
Male And Female Rats ◽  
Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

scholarly journals Chronic Ethanol Exposure during Adolescence Increases Voluntary Ethanol Consumption in Adulthood in Female Sprague Dawley Rats

2020 ◽  
Vol 10 (12) ◽  
pp. 900
Author(s):  
Antoniette M. Maldonado-Devincci ◽  
Cheryl L. Kirstein
Keyword(s):  
Alcohol Use ◽  
Chronic Exposure ◽  
Ethanol Exposure ◽  
Chronic Ethanol ◽  
Female Rats ◽  
Saccharin Intake ◽  
Male And Female ◽  
Chronic Ethanol Exposure ◽  
Male And Female Rats

Early alcohol use is a major concern due to the dramatic rise in alcohol use during adolescence. In humans, adolescent males and females consume alcohol at equivalent rates; however, in adulthood males are more likely to consume harmful levels of alcohol. In animal models, the long-term dose-dependent and sex-dependent effects of alcohol exposure during adolescence have not been readily assessed relative to exposure that is initiated in adulthood. The purpose of the present set of experiments was to determine if adolescent exposure to chronic ethanol would predispose male and female rats to greater ethanol intake in adulthood when compared to animals that were not exposed to chronic ethanol exposure until early adulthood. Male and female rats were chronically administered 0.75 g/kg or 1.5 g/kg ethanol or saline for 21 days during adolescence (postnatal day (PND) 30–50) or adulthood (PND 60–80). All rats subsequently underwent 14-days of abstinence (PND 51–64 or PND 81–94, respectively). Finally, all rats were given 30-min daily access to saccharin-sweetened ethanol or saccharin alone from PND 65–80 for adolescent-exposed rats and PND 95–110 for adult-exposed rats. Exposure to 0.75 g/kg ethanol did not alter ethanol or saccharin intake in adolescent-exposed or adult-exposed rats, regardless of sex. In contrast, chronic exposure to the higher 1.5 g/kg dose during adolescence increased ethanol intake in adulthood in female rats. However, there was no change in saccharin intake in animals exposed to 1.5 g/kg ethanol during adolescence or adulthood, regardless of sex. Additionally, there were no clear age- and ethanol-dependent changes in duration of loss of righting reflex and blood ethanol concentrations to a challenge administration of a higher dose of ethanol. The results of the present set of experiments indicate chronic exposure to a high dose of ethanol during adolescence in female rats did indeed predispose rats to consume more ethanol in adulthood. Given that these effects were only observed in adolescent-exposed female rats, these results support a unique vulnerability to the long-term consequences of adolescent ethanol exposure in female rats, an effect that is not merely mediated by the sweetener used in the ethanol solution.

scholarly journals Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Sang Hyun Park ◽  
Kannampalli Pradeep
Keyword(s):  
Clinical Trials ◽  
Small Intestine ◽  
Oral Administration ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Phase Ii Clinical Trials ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

scholarly journals Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

2006 ◽  
Vol 28 (2) ◽  
pp. 238-244 ◽  
Author(s):  
Joaquin N. Lugo ◽  
Marlene A. Wilson ◽  
Sandra J. Kelly
Keyword(s):  
Ethanol Exposure ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259446
Author(s):  
Jocelyn Rivera-Ortiz ◽  
Jessalyn Pla-Tenorio ◽  
Myrella L. Cruz ◽  
Krystal Colon ◽  
Jaileene Perez-Morales ◽  
...  
Keyword(s):  
Small Intestine ◽  
Female Rats ◽  
Sprague Dawley ◽  
Beta Adrenergic ◽  
Male And Female ◽  
Blood Brain ◽  
Male And Female Rats ◽  
Junction Protein ◽  
Systemic Pathology ◽  
Hiv 1

Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neurotoxic effects leading to neurological damage, learning impairment, and immune upregulation that induces inflammation in the lungs and small intestine (SI). In this follow-up study, we focus on the sympathetic nervous system (SNS) as the important branch for peripheral inflammation resulting from astrocytic Nef expression. Male and female Sprague Dawley rats were infused with transfected astrocytes to produce Nef. The rats were divided in four groups: Nef, Nef + propranolol, propranolol and naïve. The beta-adrenergic blocker, propranolol, was administered for 3 consecutive days, starting one day prior to surgery. Two days after the surgery, the rats were sacrificed, and then blood, brain, small intestine (SI), and lung tissues were collected. Levels of IL-1β were higher in both male and female rats, and treatment with propranolol restored IL-1β to basal levels. We observed that Nef expression decreased staining of the tight junction protein claudin-5 in brain tissue while animals co-treated with propranolol restored claudin-5 expression. Lungs and SI of rats in the Nef group showed histological signs of damage including larger Peyer’s Patches, increased tissue thickness, and infiltration of immune cells; these findings were abrogated by propranolol co-treatment. Results suggest that interruption of the beta adrenergic signaling reduces the peripheral organ inflammation caused after Nef expression in astrocytes of the brain.

scholarly journals Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

2020 ◽  
Vol 59 (5) ◽  
pp. 531-538
Author(s):  
Sylvia E West ◽  
Jonathan C Lee ◽  
Tinika N Johns ◽  
Elizabeth A Nunamaker
Keyword(s):  
Rattus Norvegicus ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Withdrawal Reflex ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Laboratory Rodent ◽  
Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

Administration of ursolic acid to new-born pups prevents dietary fructose-induced non-alcoholic fatty liver disease in Sprague Dawley rats

2020 ◽  
pp. 1-12
Author(s):  
Nyasha C. Mukonowenzou ◽  
Rachael Dangarembizi ◽  
Eliton Chivandi ◽  
Pilani Nkomozepi ◽  
Kennedy H. Erlwanger
Keyword(s):  
Fluid Intake ◽  
Female Rats ◽  
Surrogate Markers ◽  
Sprague Dawley ◽  
Alcoholic Fatty Liver ◽  
Male And Female ◽  
Hepatic Lipid Accumulation ◽  
Male And Female Rats ◽  
Dietary Fructose ◽  
Alcoholic Fatty Liver Disease

Abstract Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21–P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

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