scholarly journals Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

2018 ◽  
Author(s):  
Jacques D. Nguyen ◽  
K. M. Creehan ◽  
Tony M. Kerr ◽  
Michael A. Taffe
Keyword(s):  
Propylene Glycol ◽  
Radio Telemetry ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Self Administration ◽  
Male And Female ◽  
Male Adolescents ◽  
Male And Female Rats ◽  
Adolescent Groups

AbstractAdolescents are regularly exposed to Δ9-tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference. Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl self-administration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood.AbbreviationsPG, propylene glycol; THC, Δ9tetrahydrocannabinol;

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

scholarly journals Tolerance to hypothermic and antinoceptive effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in rats

2017 ◽  
Author(s):  
Jacques D. Nguyen ◽  
Yanabel Grant ◽  
Tony M. Kerr ◽  
Arnold Gutierrez ◽  
Maury Cole ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Wistar Rats ◽  
Female Rats ◽  
Male Rats ◽  
Preclinical Studies ◽  
Male And Female ◽  
Temperature Changes ◽  
Male And Female Rats ◽  
Antinociceptive Effects ◽  
Female Wistar Rats

AbstractRationaleA reduced effect of a given dose of Δ9-tetrahydrocannabinol (THC) emerges with repeated exposure to the drug. This tolerance can vary depending on THC dose, exposure chronicity and the behavioral or physiological measure of interest. A novel THC inhalation system based on e-cigarette technology has been recently shown to produce the hypothermic and antinociceptive effects of THC in rats.ObjectiveTo determine if tolerance to these effects can be produced with repeated vapor inhalation.MethodsGroups of male and female Wistar rats were exposed to 30 minutes of inhalation of the propylene glycol (PG) vehicle or THC (200 mg/mL in PG) two or three times per day for four days. Rectal temperature changes and nociception were assessed after the first exposure on the first and fourth days of repeated inhalation.ResultsFemale, but not male, rats developed tolerance to the hypothermic and antinociceptive effects of THC after four days of twice-daily THC vapor inhalation. Thrice daily inhalation for four days resulted in tolerance in both male and female rats. The plasma THC levels reached after a 30 minute inhalation session did not differ between the male and female rats.ConclusionsRepeated daily THC inhalation induces tolerance in female and male rats, providing further validation of the vapor inhalation method for preclinical studies.AbbreviationsPG, propylene glycol; THC; Δ9tetrahydrocannabinol;

scholarly journals Dietary cottonseed consumption induced subfertility in male and female rats: a potent eco-friendly rodenticide compound

2021 ◽  
Author(s):  
Fariborz Nowzari ◽  
Farhad Rahmanifar ◽  
Nader Tanideh ◽  
Mohammad Reza Dorvash ◽  
Arezoo Khoradmehr ◽  
...  
Keyword(s):  
Treatment Group ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Control Group ◽  
Cottonseed Flour ◽  
Male And Female ◽  
Treatment Groups ◽  
Male And Female Rats ◽  
Significant Difference

Abstract Effects of cottonseed flour in male and female rats’ fertility based on hormonal and histomorphometry changes were studied. Sixty-four Sprague-Dawley adult male and female rats were randomly divided into control and treatment groups. Treatment group was received diets containing cottonseed flour for 35 days. Control group was given standard rat food. Body and testis weights, epididymis semen evaluation indices and serum sex steroid hormones were determined. Histomorphometry alterations of testes and ovary were evaluated. Then, normal female and male rats were mated by rats in both groups and after 35 days, number of pups was measured. However, there was no significant difference in whole body and testes weights, sperm concentration and viability between the control and treatment groups, respectively. Moreover, sperm motility in the treatment rats was significantly lower than the control group. Serum hormones alterations were not significant, but histomorphometry evaluations of testes showed significant changes in the testis structures after chronic consumption of cottonseed flour. In the female rats, body weight did not have significant difference between the treatment and control groups. Histomorphometry data in female ovary showed significant reduction of primary follicle volume and number in the treatment group against control. Follicle stimulating hormone showed insignificant reduction in the treatment group. Number of pups was significantly reduced in the female rats fed by cottonseed flour. Cottonseed flour in rat diet had adverse effects on rat reproduction. Therefore, it can be used as an efficient product for control of the rat population as a natural rodenticide agent.

scholarly journals Relapse to cotinine seeking in rats: Differential effects of sex

2021 ◽  
Author(s):  
Xiaoying Tan ◽  
Elizabeth Neslund ◽  
Zheng-Ming Ding
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Potential Mechanism ◽  
Self Administration ◽  
Drug Seeking ◽  
Male And Female ◽  
Rat Models ◽  
Significant Challenge ◽  
Male And Female Rats ◽  
Future Treatments

Relapse is a defining feature of smoking and a significant challenge in cessation management. Elucidation of novel mechanisms underlying relapse may inform future treatments. Cotinine, the major metabolite of nicotine, has been shown to support intravenous self-administration in rats, suggesting it as one potential mechanism contributing to nicotine reinforcement. However, it remains unknown whether cotinine would induce relapse-like behaviors. The current study investigated relapse to cotinine seeking in two relapse models, the reinstatement of drug seeking and incubation of drug craving models. In the reinstatement model, rats were trained to self-administer cotinine, extinguished cotinine-associated responses, and underwent cue-, drug-, or stress-induced reinstatement. Conditioned cues associated with cotinine self-administration, cotinine (1-2 mg/kg), or the pharmacological stressor yohimbine (1.25-2.5 mg/kg) reinstated cotinine seeking. Female rats displayed more pronounced cue-induced, but not drug- or stress-induced reinstatement than male rats. In addition, an overall analysis revealed that female rats exhibited greater cotinine self-administration, but less extinction than male rats. In the incubation model, rats were trained to self-administer cotinine, and underwent forced withdrawal in home cages. Rats were tested for cue-induced cotinine seeking on both withdrawal day 1 and withdrawal day 18. Rats exhibited greater cotinine-seeking on withdrawal day 18 compared to withdrawal day 1, with no difference between male and female rats. These findings indicate that cotinine induces sex-dependent relapse to cotinine seeking in rats, suggesting that cotinine may be a novel mechanism contributing to relapse. These rat models are valuable preclinical tools for interrogation of neurobiological underpinnings of relapse to cotinine seeking.

Thirteen-Week Oral Toxicity Study of l-Arginine in Rats

2004 ◽  
Vol 23 (2) ◽  
pp. 101-105 ◽  
Author(s):  
Shoji Tsubuku ◽  
Kazuhisa Hatayama ◽  
Kazunori Mawatari ◽  
Miro Smriga ◽  
Takeshi Kimura
Keyword(s):  
Amino Acid ◽  
Group Treatment ◽  
Clinical Signs ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Standard Diet ◽  
Male And Female ◽  
Cell Counts ◽  
Male And Female Rats

The amino acid l-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% ( w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/ w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% ( w/w) for both genders (males, 3.3 ±0.1 g/kg/day; females, 3.9 ±0.2 g/kg/day).

scholarly journals Histological and Hormonal Study of the Protective Effect of the Calotropis Procera Against the Toxicity of Mercury Chloride

2020 ◽  
pp. 5-14
Author(s):  
Leila Belfarhi ◽  
Ibtissem Chouba ◽  
Naziha Amri ◽  
Nadia Boukris ◽  
Abdelkrim Tahraoui
Keyword(s):  
Mercuric Chloride ◽  
Female Rats ◽  
Male Rats ◽  
Calotropis Procera ◽  
Control Group ◽  
Mercury Chloride ◽  
Protective Effects ◽  
Male And Female ◽  
Male And Female Rats ◽  
Group I

We undertook this study with the aim of investigating the detoxification of an extreme toxic metal mercury chloride by the Calotropis procera plant taken from the Algerian Sahara. We studied the protective effects of the plant Calotropis procera against renal toxicity and Mercury chloride-induced hepatic. Ten male and female albino rats Wistar were divided into four equal groups. Group (I) served as a healthy control group, group (II) were intra-peritoneal administered with 10 ml of Calotropis procera, group (III) were intra-peritoneal administrated with both 10 ml of the plant Calotropis procera and 0.2 mg of mercuric chloride (HgCl2) and group (IV) were intraperitoneal administrated with both 0.2 mg of mercuric chlorid (HgCl2) and 10 ml of the plant Calotropis. All groups were treated for 20 days. Mercury chloride causes a slight increase in glomerular cellularitis in the kidneys of male and female rats. Treatment with Calotropis procera had significantly improving protective effects of kidney of female rats from toxicity of mercuric chloride. Calotropis procera causes a thyroid-like appearance in the glomeruli of the male kidneys to hide the lesions of mercury chloride. Our results have shown that the plant Calotropis procera completely protects the liver of female rats against the toxicity of mercury chloride. In the liver of male rats, mercury chloride causes macro-vacuolar steatosis. Treatment with Calotrpois procera hid the hepatic steatosis of male rats and centralized them in the center under the aspect of peri-centro-lobular medio-vacuolar steatosis. Mercuric chloride caused a decrease in the secretion of the hormone ACTH in the group of male and female rats. Treatment with Calotropis procera caused increased ACTH levels in female rats and did not cause ACTH changes in male rats. Our results demonstrate from hormone analyzes of the hormone ACTH that female rats are resistant more than male rats via the toxicity of mercury chloride.

scholarly journals Study on the Optimization and Stability of Single-dose Streptozotocin-induced Diabetic Modelling in Rats

2021 ◽  
Author(s):  
Yao Zhang ◽  
Jiao Zhang ◽  
Ming Hong ◽  
Jingyi Huang ◽  
Rui Wang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Fat ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
And Control

Abstract Aim: This study was performed to optimize the experimental conditions in streptozotocin (STZ)-induced diabetic model by using Sprague-Dawley (SD) rats to evaluate the stability of the model.Methods: In addition to the control group, the male and female SD rats were randomly divided into the following treatment groups (with six rats per group): STZ 45 (45 mg/kg STZ); STZ 65 (65 mg/kg STZ); STZ 85 (85 mg/kg STZ); high-fat diet with STZ 45; high-fat diet with STZ 65; and high-fat diet with STZ 85. Changes in the body weight and blood glucose were observed dynamically. Results: No significant differences were found in the blood glucose or body weight between the STZ 45 and control groups in both male and female rats, whether or not the rats were on a high-fat diet. However, significant differences were found in the blood glucose between the high-dose STZ and control groups in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P<0.05 or P<0.01). Compared with the control group, significant differences in the blood glucose levels (P<0.05 or P<0.01) and higher blood glucose levels were found in the male rats fed with normal diet than those of rats fed with high-fat diet.Conclusions: In this study, male rats fed with ordinary feed and injected with 65 mg/kg STZ were the most stable and ideal diabetic rats.

scholarly journals Functional food promotes digestive functions and healthy growth of animals nurtured in confinement

2020 ◽  
Vol 44 (1) ◽  
pp. 76-88
Author(s):  
A. Ajibola ◽  
K. H. Erlwanger
Keyword(s):  
Tap Water ◽  
Nutrient Utilization ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Control Infant ◽  
Male And Female ◽  
Male And Female Rats ◽  
Healthy Growth

In the study, the growth pattern, morphometric and morphological changes in the gastrointestinal tract of growing male and female Sprague-Dawley rats fed crude honey (CH)-supplemented diets as measures of nutrient utilization, digestive functions and healthy growth were investigated. Thirty-five suckling (7-day old male and female) rats were fed CH either as low (10mLkg-1 BW) or high (20mLkg-1 BW) dose daily via stomach tube for 14 days, while the control group was gavaged with distilled water. Rats were kept with their dams to nurse freely between gavages. On weaning, CH was mixed with commercial rat feed as low (20%) or high, 50% (volume/weight, v/w), while 20% (v/w) tap water was added to the control diet. The feed intake of honey-fed male rats and control (infant: 6 – 10g; adult:31 – 38g) was significantly higher (p < 0.05) than their high dose-diet mates (infant: 5 – 8g; adult: 31 – 38g). All the rats were killed at 13 weeks old for gross and microscopic measurements of the abdominal viscera. Grossly, there were no significant differences (p ≥ 0.05) in the relative lengths (%BW) and weight: length ratio (g cm-1 ) of the small and large intestines in both sexes. Crude honey increased the absolute and relative weights of the caecum (1.73 ± 0.05g; 0.38 ± 0.02%BW) and pancreas (2.52 ± 0.11g; 0.55 ± 0.03%BW), with significant influence (p<0.05) in the male rats. In addition, dietary inclusion of CH at low dose enhanced intestinal villi growth in height (84.0 ± 4.0µm) and width (25.2 ± 1.5µm). Dietary supplementation with crude honey also enhanced body weight gain of male rats (495.52 ± 8.98g) and females (242.52 ± 6.87g), improved abdominal organs' functional size: liver (10.92 ± 0.32g; 2.72 ± 0.13%BW); spleen (1.25 ± 0.06g; 0.27 ± 0.02%BW), devoid of pathological changes, as shown by liver histomorphology (1.2 ± 0.3) and normal hepatocellular architecture thereby conferring nutritional and health benefits on animals nurtured in confinement.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

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