scholarly journals Sex and metabolic state interact to influence expression of passive avoidance memory in rats: Potential contribution of A2 noradrenergic neurons

2021 ◽  
Author(s):  
Caitlyn M. Edwards ◽  
Tyla Dolezel ◽  
Linda Rinaman

AbstractCompeting motivational drives coordinate behaviors essential for survival. For example, interoceptive feedback from the body during a state of negative energy balance serves to suppress anxiety-like behaviors and promote exploratory behaviors in rats. Results from past research suggest that this shift in motivated behavior is linked to reduced activation of specific neural populations within the caudal nucleus of the solitary tract (cNTS). However, the potential impact of metabolic state and the potential role of cNTS neurons on conditioned avoidance behaviors has not been examined. The present study investigated these questions in male and female rats, using a task in which rats learn to avoid a context (i.e., a darkened chamber) after it is paired with a single mild footshock. When rats later were tested for passive avoidance of the shock-paired chamber, male rats tested in an overnight food-deprived state and female rats (regardless of feeding status) displayed significantly less avoidance compared to male rats that were fed ad libitum prior to testing. Based on prior evidence that prolactin-releasing peptide (PrRP)-positive noradrenergic neurons and glucagon-like peptide 1 (GLP1)-positive neurons within the cNTS are particularly sensitive to metabolic state, we examined whether these neural populations are activated in conditioned rats after re-exposure to the shock-paired chamber, and whether neural activation is modulated by metabolic state. Compared to the control condition, chamber re-exposure activated PrRP+ noradrenergic neurons and also activated neurons within the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST), which receives dense input from PrRP+ terminals. In parallel with sex differences in passive avoidance behavior, PrRP+ neurons were less activated in female vs. male rats after chamber exposure. GLP1+ neurons were not activated in either sex. Overnight food deprivation before chamber re-exposure reduced activation of PrRP+ neurons, and also reduced vlBNST activation. Our results support the view that PrRP+ noradrenergic neurons and their inputs to the vlBNST contribute to the expression of passive avoidance memory, and that this contribution is modulated by metabolic state.

1951 ◽  
Vol 7 (3) ◽  
pp. 271-279 ◽  
Author(s):  
J. T. EAYRS

The growth of the body and central nervous system and the emergence of stereotyped behaviour have been studied in male and female rats during the first 24 days of life. The effects of daily injections of equine gonadotrophin on these measures have also been investigated. The weight of the body and of the central nervous system was significantly less in the female than in the male. The daily administration of 10 i.u. of equine gonadotrophin was without effect on either. The movements of the trunk and limbs concerned in the body-righting reflex became coordinated more slowly in the gonadotrophin-injected animals than in their litter-mate controls. At 15 days old, male rats were able to right in mid-air more successfully than litter-mate females. The placing reflex appeared earlier in the male than in the female. Its appearance was accelerated in the females given gonadotrophin, but not in the males. In the ventral funiculus of the spinal cord of 24-day-old experimental animals, the axis cylinders occupied more space relative to that occupied by myelin than did those of the controls. The total amount of myelin present was unchanged. There was no sex difference in the progress of myelination in the spinal cord. The significance of these findings in relation to the secretion of sex hormones is discussed. It is suggested that the secretion of androgen may be responsible for an acceleration of nervous maturation.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rupesh Shirodkar ◽  
Chandrasekhar Misra ◽  
Chethan GH ◽  
Pallavi Shetty ◽  
Zenab Attari ◽  
...  

The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  

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.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

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.


1983 ◽  
Vol 64 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Maurizio Muraca ◽  
Jan De Groote ◽  
Johan Fevery

1. Hepatic bilirubin UDP-glucuronosyltransferase activity was higher in female than in male rats; gonadectomy decreased enzyme activity in females and increased it in males. This sex difference in bilirubin conjugation was further used to evaluate the effect of differences in conjugation on the maximal biliary excretion of bilirubin in the non-anaesthetized rat. 2. After infusion of bilirubin, the maximal biliary excretory rate (Tm) and maximal concentration of bilirubin in bile were respectively 70% and 40% higher in female than in male rats; these values were decreased in females after ovariectomy and increased in males after orchiectomy. A linear relationship was found (r = 0.86; P < 0.001) between bilirubin Tm and hepatic bilirubin UDP-glucuronosyltransferase activity in the four groups of rats, suggesting that conjugation was the rate-limiting step for the maximal hepatic transport of bilirubin. 3. At the end of bilirubin infusion, bilirubin conjugates in serum, determined by alkaline methanolysis and high-performance liquid chromatography, ranged from 0.5 to 1.4% of total bilirubin. Therefore no significant reflux of conjugated bilirubin occurred during saturation of the hepatic transport of the pigment, once more suggesting that the secretory step was not rate-limiting. 4. The composition of bilirubin conjugates in bile was similar in the four groups of rats, despite significant differences in transferase activity. This suggests that the relative proportion of bilirubin mono- and di-conjugates in bile is affected by factors other than transferase activity alone. Relatively more monoconjugates were excreted under the bilirubin load than in basal conditions.


1972 ◽  
Vol 53 (1) ◽  
pp. 47-57 ◽  
Author(s):  
C. M. TAPPER ◽  
F. NAFTOLIN ◽  
K. BROWN-GRANT

SUMMARY The changes in plasma luteinizing hormone (LH) concentration during the first few days after ovariectomy in the rat differ according to the stage of the cycle at which the operation is performed. When carried out at oestrus there was no increase in LH concentration in the first 4 days. After operation at metoestrus the concentration was increased at 3 days but not earlier. Ovariectomy at dioestrus resulted in an immediate increase after 8 h, a subsequent fall, though not to basal levels, and a fairly steady rise thereafter. Ovariectomy at pro-oestrus produced a very large initial rise in plasma LH which probably represents an accelerated release of the ovulatory surge of LH rather than a specific response to ovariectomy. At 24 h after ovariectomy at pro-oestrus levels were below normal and did not increase again for a further 3 days. In contrast, male rats showed a rapid and sustained rise in plasma LH concentration after castration. It is suggested that the different patterns seen in the female may be related to the time that elapsed since the hypothalamo—pituitary system was exposed to high levels of circulating oestradiol. The changes in plasma LH concentration observed after ovariectomy in neonatally androgen-treated rats, rats in persistent oestrus due to exposure to constant light, and rats in early pregnancy are consistent with this hypothesis. Differing responses to the administration of sodium pentobarbitone between male and female rats even 21 days after gonadectomy suggest that there may also be differences in this negative feedback system between the two sexes that are independent of the nature of the gonadal steroid secreted.


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