scholarly journals 7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse
Keyword(s):  
Body Weight ◽  
Progressive Ratio ◽  
Ethanol Exposure ◽  
Ethanol Solution ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Bdnf Expression ◽  
Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

scholarly journals Dietary Exposure to Oxidized Frying Oil from Fetus to Adulthood Suppresses Male Reproductive Development by Altering Testicular Cholesterol and Testosterone Homeostasis in Sprague Dawley Rats

2020 ◽  
Vol 150 (7) ◽  
pp. 1713-1721
Author(s):  
Hai-Ping Wu ◽  
Yu-Shun Lin ◽  
Chi-Fen Chang ◽  
Shui-Yuan Lu ◽  
Pei-Min Chao
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Soybean Oil ◽  
Body Weight Loss ◽  
Reproductive Development ◽  
Frying Oil ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

ABSTRACT Background Dietary frying oil may have endocrine-disrupting effects, as a feminization effect was observed in cohorts of C57BL/6J male mice fetuses from dams consuming oxidized frying oil (OFO) during pregnancy. Objective The aim of present study was to test the hypothesis that OFO is an anti-androgen. Methods In experiment 1, male progeny of Sprague Dawley female rats fed fresh oil or an OFO diet (10 g fat/100 g, from fresh or 24-h–fried soybean oil; [control diet (C) and OFO groups, respectively] from midgestation through lactation were studied. Pups were weaned at 3 wk of age and then consumed their mothers’ diet until 9 wk of age. In addition, a group of dams and pups that consumed a high-fat diet (HF; 10 g fried and 20 g fresh soybean oil/100 g) was included to counteract body-weight loss associated with OFO ingestion. Indices of male reproductive development and testosterone homeostasis were measured. In experiment 2, male rats were allocated to C and OFO groups (treated as above) and indices of male fertility compared at 9–10 wk of age. Results In experiment 1, final body weights of the HF group were lower (17%) than the C group but higher (14%) than the OFO group (P < 0.0001 for each). In addition to abnormalities in seminiferous tubules, HF and OFO groups did not differ from one another, but, compared with the C group, had delayed preputial separation (4.9 d) and reductions in serum testosterone concentrations (17–74%), anogenital distance (8–20%), weights of androgen-dependent tissues (8–30%), testicular testosterone and cholesterol concentrations (30–40%), and mRNA levels of genes involved in steroidogenesis and cholesterol homeostasis (30–70%). In experiment 2, OFO-exposed males had 20% lower sperm motility (P < 0.05); however, when mated to normal females, pregnancy rates and litter sizes did not differ between OFO and C groups. Conclusions The anti-androgenic effect of OFO in Sprague Dawley rats was attributed to decreased testicular concentrations of cholesterol (testosterone precursor) and not body-weight loss.

Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats

2014 ◽  
Vol 33 (5) ◽  
pp. 393-402 ◽  
Author(s):  
Richard A. Angerhofer ◽  
Mark W. Michie ◽  
Glenn J. Leach ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Sulfur Mustard ◽  
Female Rats ◽  
Male Rats ◽  
Control Individual ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.

scholarly journals Evaluation of acute and sub-acute oral toxicity of the aqueous extract of Aquilaria malaccensis leaves in Sprague Dawley rats

2019 ◽  
pp. 20-32
Author(s):  
Redzuan Nul Hakim Abdul Razak ◽  
Suzanah Abdul Rahman ◽  
Asmah Hanim Hamdan ◽  
Roszaman Ramli ◽  
Muhammad Lokman Md Isa ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Toxicity ◽  
Lethal Dose ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Histopathological Analysis ◽  
Sprague Dawley ◽  
Aquilaria Malaccensis ◽  
Sprague Dawley Rats

Aquilaria malaccensis or commonly known as ‘gaharu’ is a species of Aquilaria genus and belongs to the Thymelaeaceae family. It is widely distributed in Malaysia, Indonesia, and the Borneo Islands. Traditionally, its leaves were used to relieve bruises and studies have shown that they function as an antioxidant, aphrodisiac, and tranquilizer. Despite its proven beneficial medicinal properties, information regarding its toxicity is limited. Therefore, we performed a safety evaluation on the aqueous A. malaccensis leaves extract (AMAE) in Sprague Dawley rats. The assessment of acute toxicity based on the Organization for Economic Cooperation and Development (OECD) Guideline 420 revealed that AMAE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 2000 mg/kg body weight. In the sub-acute toxicity, all doses did not significantly modify the body weight and food and water intake. In male rats treated with 2000 mg/kg, there was a significant reduction in the relative weight of liver. Not only that, an increase in alkaline phosphatase and alanine transaminase was also observed in different groups among the female rats. A significant decrease in the creatinine level was also seen among male rats administered with different doses of AMAE. In both sexes, histopathological analysis had shown abnormalities in the liver and kidney of rats treated at the dose of 2000 mg/kg. In conclusion, the 50% lethal dose (LD50) of AMAE was estimated to be greater than 2000 mg/kg. In sub-acute duration, the findings suggested that AMAE administered orally is slightly toxic at higher doses (2000 mg/kg) and could provoke functional and structural changes in the kidney and liver of rats. Thus, the extract should be used with caution.

scholarly journals THE EFFECT OF SECANG EXTRACT (CAESALPINIA SAPPAN LINN) ON THE WEIGHT AND HISTOLOGY APPEARANCE OF WHITE MALE RATS’ HEARTS INDUCED BY ISOPROTERENOL

2017 ◽  
Vol 9 ◽  
pp. 59
Author(s):  
Kristiana Nugraheni ◽  
Fadlina Chany Saputri
Keyword(s):  
Myocardial Infarction ◽  
Body Weight ◽  
White Male ◽  
Negative Control ◽  
Male Rats ◽  
Heart Cells ◽  
Sprague Dawley ◽  
Macroscopic Appearance ◽  
Caesalpinia Sappan ◽  
Sprague Dawley Rats

Objective: This study was conducted to determine the cardioprotective effect of secang extract on the heart cells of rats who suffered from myocardialinfarction induced by isoproterenol.Materials and Methods: Sprague Dawley rats were divided into six groups: Normal control, negative control, control extract (200 mg/kg), and threedifferent dose extract groups (50, 100, and 200 mg/kg body weight) that were given treatment for 30 days, and then, induced with isoproterenol.Observations were made for changes in the macroscopic appearance, cardiac weight, and histology of the cardiac organ.Results: The results showed a decrease in the incidence of myocardial infarction in rats given secang extract. The infarction area decreased withincreasing doses of extract. The weight of the heart in the control extract group was smaller than in the negative control group.Conclusions: Damage to heart cells, seen in the microscope, decreased with increasing doses.

SUBCHRONIC TOXICITY OF MALAYSIAN ACALYPHA INDICA: BIOCHEMISTRY AND HAEMATOLOGY ANALYSIS OF RAT

2016 ◽  
Vol 78 (5-5) ◽  
Author(s):  
Norazlanshah Hazali ◽  
Nurul Nadia Mohd Nazri ◽  
Muhammad Ibrahim ◽  
Mashita Masri
Keyword(s):  
Body Weight ◽  
Skin Diseases ◽  
Female Rats ◽  
Control Group ◽  
Dosage Group ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
High Dosage Group ◽  
Sprague Dawley Rats ◽  
Acalypha Indica

Acalypha indica is one of the medicinal plants that have been used since ages to treat various diseases such as pneumoniae, asthma and skin diseases. This study aimed to explore the subchronic toxicity effect of Acalypha indica on Sprague Dawley rats based on haematological and biochemical parameters. The extract of Acalypha indica was prepared by aqueous extraction technique. 48 Sprague Dawley rats aged 7 weeks, weighing 150-200g were randomly divided into four groups, 6 animals per gender. A control group received water vehicle while three treated groups received the extract at dosage of 100 (low dosage group), 200 (medium dosage group) and 300 (high dosage group) mg/kg body weight. The sample was administered orally by using oral gavage daily for 90 days. No sign of toxicity and mortality was recorded in all groups throughout the study. There were no significant different (p>0.05) in body weight gain, food and water intake between control and treatment group. However, there was significant different in uric acid between control and high dosage group of male and female rats but the mean were in normal range. There were also reduced in mean of urea and creatinine in all dosage group of male and urea for all dosage group of female. Statistically significant reduced in urea was recorded between control and high dosage group of male only. Other parameters showed no significant different between control and treatment groups. Therefore, Acalypha indica is safe for human consumption and might be potential in reducing kidney damage problem.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Estrous Cycle ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Female Rats ◽  
Male Rats ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Tension Development ◽  
Sprague Dawley Rats

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

scholarly journals Some nutritional properties of unrefined sugar and its promotion of the survival of new-born rats

1985 ◽  
Vol 54 (3) ◽  
pp. 593-603 ◽  
Author(s):  
Eisa Omer Ahmed ◽  
Yudkin John
Keyword(s):  
Fatty Acid Synthetase ◽  
Female Rats ◽  
Male Rats ◽  
Blood Cholesterol ◽  
Maize Starch ◽  
Sprague Dawley ◽  
Brown Sugar ◽  
Sprague Dawley Rats ◽  
Male Wistar Rats ◽  
Glucose 6 Phosphate Dehydrogenase

1. The claims that rats fed on diets with ‘brown sugar’ (unrefined muscovado) perform better in a number of ways than do rats fed on refined white sugar (sucrose) have been examined.2. Male Wistar rats were fed on purified diets from weaning, in which the carbohydrate component was either maize starch or unrefined sugar or sucrose. The sugars produced no differences in growth rate, body composition, or the weights of liver or kidneys. Compared with sucrose, unrefined sugar produced an increase in blood cholesterol and in the activity of hepatic fatty acid synthetase, and a greater increase in blood triglyceride. In confirmation of earlier results, rats fed on either sugar had heavier livers and kidneys, increased activity of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and a higher concentration of plasma triglyceride compared with rats fed on maize starch.3. Female Sprague-Dawley rats were fed on the same three diets as the male rats, and mated when they weighed about 200 g. No difference was seen in their ability to mate, the progress of pregnancies, or the sizes of the litters. Does fed on unrefined sugar produced litters of higher viability than did does fed on starch or sucrose. Survival was between 85 and 100% with unrefined sugar and between 30 and 75% with starch or sucrose.4. Unrefined muscovado sugar has thus been shown to contain a factor required by female rats for the proper viability of their pups. This may be the same ‘Reproductive Factor R’ as that described by Wiesner & Yudkin (1951). In certain circumstances, unrefined muscovado sugar might therefore contribute to the nutritional value of a human diet, although in what circumstances, in what respect and to what extent it might do so, is by no means clear.

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.

Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
Nancy L Howell ◽  
Robert M Carey
Keyword(s):  
Receptor Activation ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Angiotensin Iii ◽  
Compound 21 ◽  
Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

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