scholarly journals Anoxia at Birth Induces Behaviorally-Relevant Changes in alpha2-Noradrenergic Receptor Binding in the Adult Rat

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Wayne G. Brake ◽  
Shakti Sharma

Evidence suggests that Caesarean section birth in the rat, with or without an additional period of anoxia, results in long-term changes in brain catecholamine levels as well as reactivity to stress. The purpose of the present investigation was to determine whether Caesarean birth plus anoxia alters (alpha)2-noradrenergic receptor binding and sensitivity to the (alpha)2 receptor agonist, clonidine, in the Porsolt forced swim test. Sprague Dawley rat dams were decapitated and the uteruses were removed by Caesarean section. Pups were then delivered either immediately (Caesarean Only group), or were immersed in a saline bath for approximately 15 minutes (Caesarean plus Anoxia group) before delivery of the pups. A third group of animals born vaginally served as controls (Vaginally-born group). Four to five months postnatally, the expression of (alpha)2 receptors was measured by receptor autoradiography using [3H]-Rauwolscine binding. Receptor binding was increased in the area of the ventral hypothalamus and decreased in the CA1 region of the hippocampus in animals subjected to Caesarean plus Anoxia at birth. These animals also displayed a subsensitive response to the immobilizing effects of clonidine (100 micrograms/kg, i.p.) in the Porsolt forced swim test. Specifically these data show that Caesarean birth produces long-term changes in (alpha)2 receptor density and that, in animals subjected to Caesarean plus anoxia, these changes are reflected in a behavioral subsensitivity to the (alpha)2 agonist, clonidine. The findings reported here provide further experimental support for the hypothesis that birth complications may contribute to the pathophysiology of disorders such as schizophrenia that involve central catecholamine dysfunction.

2020 ◽  
Author(s):  
Palesa Mosili ◽  
Bongeka Cassandra Mkhize ◽  
Phikelelani Ngubane ◽  
Ntethelelo Sibiya ◽  
Andile Khathi

Abstract Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.


2020 ◽  
Author(s):  
Palesa Mosili ◽  
Bongeka Cassandra Mkhize ◽  
Phikelelani Ngubane ◽  
Ntethelelo Sibiya ◽  
Andile Khathi

Abstract Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model. Methods: Sprague Dawley Rats were randomly divided into non-prediabetic group (NPD) and pre-diabetic group (PD) (n=6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, insulin resistance using the HOMA-IR index, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test (FST) were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were measured too. Results: Impaired glucose handling in the PD group as well as increase in corticosterone (CORT) was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed underwent the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group. Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.


Author(s):  
Roni Yankelevitch-Yahav ◽  
Motty Franko ◽  
Avrham Huly ◽  
Ravid Doron

2021 ◽  
Vol 165 ◽  
pp. 56-57
Author(s):  
Shota Naoe ◽  
Takahiro Kataoka ◽  
Hina Shuto ◽  
Junki Yano ◽  
Tetsuya Nakada ◽  
...  

2019 ◽  
Vol 236 (11) ◽  
pp. 3353-3362 ◽  
Author(s):  
Mohammad Nasehi ◽  
Mohammad-Hossein Mohammadi-Mahdiabadi-Hasani ◽  
Mohaddeseh Ebrahimi-Ghiri ◽  
Mohammad-Reza Zarrindast

2021 ◽  
pp. 1-7
Author(s):  
Dylan J. Terstege ◽  
Debra S. MacDonald ◽  
R. Andrew Tasker

Abstract Objective: Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Methods: Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot. Results: One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression. Conclusions: We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.


2021 ◽  
pp. 026988112199688
Author(s):  
Eduardo R Butelman ◽  
Caroline Baynard ◽  
Bryan D McElroy ◽  
Thomas E Prisinzano ◽  
Mary Jeanne Kreek

Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists.


Sign in / Sign up

Export Citation Format

Share Document