scholarly journals Sex differences in choice-based thermal nociceptive tasks in adult rats

2021 ◽  
Author(s):  
Justin R Bourgeois ◽  
Ashley M Kopec

Interest in the role of sex as a biological variable continues to increase, including a mandate for the study of both sexes in NIH-funded research. Choice-based thermal nociceptive tests allow for the study of a more spontaneous response to thermal stimuli and avoidance behavior compared to traditional nociceptive assays, and their usage has been increasing in recent years. However, to date no comparison of naive male and female responses to such tests has been published. As sex differences are known to exist in both human chronic pain conditions and rodent models of nociception, it is critical to understand the impact of sex on any nociceptive assay. Herein, we examined the effect of sex on two choice-based thermal nociceptive tests, the thermal gradient test and the temperature place preference test, in adult rats. We report that marked sex differences exist in responses to these tests. Namely, the activation of a 10 C-to-47 C thermal gradient results in an increase in time spent in the 10 C zone in females, compared to a reduction in males. In a temperature place preference test pairing a surface temperature of 22 C with either 5 C, 10 C, 47 C, or 50 C, males spent less than 50% of their time in every non-22 C zone, but in females this was only observed when testing 50 C. Together, these results suggest that male rats show more avoidance behavior to non-ambient temperatures when given free access to multiple zones, including at temperatures which are milder than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.

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.


Author(s):  
Ewa Zwierzyńska ◽  
Agata Krupa-Burtnik ◽  
Bogusława Pietrzak

Abstract Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.


2021 ◽  
Author(s):  
Nazanin Kahvandi ◽  
Zahra Ebrahimi ◽  
Seyed Asaad Karimi ◽  
Siamak Shahidi ◽  
Iraj Salehi ◽  
...  

Abstract Background: The nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGlu receptors) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGlu receptors, including mGlu8 receptors, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGlu8 receptor allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3 μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. Results: The results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. Conclusions: The findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and in reward pathway(s). These data suggest that mGlu8 receptor may be involved in conditioned morphine reward.


2020 ◽  
Vol 11 (5) ◽  
pp. 492-498 ◽  
Author(s):  
Letícia Chavaglia Cavalet ◽  
Larissa Cristina dos Santos Ribeiro ◽  
Gustavo Bergoli Rosa ◽  
Kássia Kristina Sousa ◽  
Aryanne Batista Soares de Melo ◽  
...  

AbstractNutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.


2021 ◽  
pp. 913-920
Author(s):  
Ľ Janovičová ◽  
B. Gromová ◽  
D. Drobná ◽  
B. Konečná ◽  
E. Renczés ◽  
...  

Extracellular DNA (ecDNA) activates immune cells and is involved in the pathogenesis of diseases associated with inflammation such as sepsis, rheumatoid arthritis or metabolic syndrome. DNA can be cleaved by deoxyribonucleases (DNases), some of which are secreted out of cells. The aim of this experiment was to describe plasma DNase activity in relation to extracellular DNA in adult rats, to analyse potential sex differences and to prove whether they are related to endogenous testosterone. Adult Lewis rats (n=28) of both sexes were included in the experiment. Male rats were gonadectomized or sham-operated and compared to intact female rats. Plasma ecDNA and DNase activity were measured using fluorometry and single radial enzyme diffusion assay, respectively. Concentrations of nuclear ecDNA and mitochondrial ecDNA were determined using real-time PCR. Females had 60% higher plasma DNase activity than males (p=0.03). Gonadectomy did not affect plasma DNase in males. Neither the concentration of total ecDNA, nor nuclear or mitochondrial DNA in plasma differed between the groups. No significant correlations between DNase and ecDNA were found. From previous studies on mice, it was expected, that male rats will have higher DNase activity. In contrast, our study in rats showed the opposite sex difference. This sex difference seems not to be caused by endogenous testosterone. Interestingly, no sex differences were observed in plasma ecDNA suggesting a complex or missing association between plasma ecDNA and DNase. The observed sex difference in plasma DNase should be taken into account in animal models of ecDNA-associated diseases.


2000 ◽  
Vol 279 (5) ◽  
pp. R1745-R1752 ◽  
Author(s):  
James B. Young

Neonatal handling permanently alters the hypothalamic-pituitary-adrenal (HPA) response to stress. Because the sympathetic nervous system (SNS) and adrenal medulla also participate in stress responses, the impact of daily handling between birth and weaning on SNS and adrenal medullary function was examined in adult rats using techniques of [3H]norepinephrine ([3H]NE) turnover and urinary catecholamine excretion. Handled animals exhibited a 23% reduction in [3H]NE turnover in heart and a 53% decrease in spleen. [3H]NE turnover in brown adipose tissue, stomach, and kidney did not differ between handled and nonhandled animals. In contrast, urinary epinephrine (Epi) excretion was significantly greater in handled rats in response to a 3-day fast than in nonhandled animals. Although body weight, weight gain in response to dietary enrichment with sucrose or lard, or body fat content did not differ in handled and nonhandled animals, handled rats displayed heavier abdominal fat depots than nonhandled animals, implying a difference in body fat distribution. Neonatal handling thus leads to decreased sympathetic activity within specific subdivisions of the SNS and, by contrast, to increased adrenal medullary responsiveness.


2019 ◽  
Vol 3 (s1) ◽  
pp. 21-21
Author(s):  
Jonathas Fernandes Queiroz Almeida ◽  
Aline Souza ◽  
Hong Ji ◽  
Kathryn Sandberg

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p <0.05), while BW in the sFR males was reduced by 12% (p<0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p<0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jonah Sydney Aprioku ◽  
Theresa Chioma Ugwu

This study investigated the effects of 30-day exposure to tobacco smoke (TS), smokeless tobacco (ST), and nicotine on reproductive parameters and oxidative biomarkers in prepubertal and adult male rats. Sperm motility was reduced by 77.5 and 89.0% in TS and ST exposed prepubertal rats and 71.1 and 86.4% in adult rats, respectively. Sperm count was also reduced by 64.7 and 89.9% in prepubertal rats and 64.9 and 47.0% in adult rats, respectively. Nicotine decreased sperm motility (82.2%) and count (62.6%) in prepubertal rats but caused no effect in adult rats. There were no changes in sperm morphology; testosterone was decreased, while LH and FSH were increased in exposed rats, when compared with control. Malondialdehyde levels in testes of exposed rats were increased, and GSH, SOD, and catalase were altered. Results indicate that subacute exposure of tobacco products alters sperm characteristics in a rank order of ST > TS > nicotine, which may be linked to increase in oxidative stress in the testis.


2021 ◽  
Author(s):  
Ana CR Ribeiro ◽  
Elisa H Hawkins ◽  
Fay M Jahr ◽  
Joseph L McClay ◽  
Laxmikant S Deshpande

Organophosphate (OP) chemicals include commonly used pesticides and also chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. While a chronic low-dose OP exposure does not produce acute cholinergic crises, epidemiological studies report long-term neuropsychiatric issues including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of a single, high-dose CPF or studied sub-chronic behavioral effects particularly the motor and cognitive effects of repeated low-dose CPF exposure. However, studies on chronic mood and depression-related morbidities following repeated sub-threshold CPF doses that would mimic occupationally-relevant OP exposures are lacking. Here, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21-days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following an 11-week washout period, CPF-treated rats exhibited a dose-dependent increase in signs of anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) despite a complete recovery of ChE activity at this stage. We speculate that both cholinergic and non-cholinergic mechanisms could play a role in the development of chronic OP-related depressive outcomes. The proposed CPF exposure paradigm could provide an ideal model to further study molecular mechanisms underlying cause and effect relationships between environmental OP exposures and the development of chronic behavioral deficits.


2021 ◽  
Vol 19 (1) ◽  
pp. 47-53
Author(s):  
Ilia Yu. Tissen ◽  
Polina A. Chepik ◽  
Andrei A. Lebedev ◽  
Leila A. Magarramova ◽  
Eugenii R. Bychkov ◽  
...  

INTRODUCTION: Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS. The aim of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration. METHODS: Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats. RESULTS: When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; p 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (p 0.05), and the number of sniffings was 2-fold increased too (p 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL. CONCLUSION: Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.


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