scholarly journals Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear-extinction Deficit

2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Wen-qin Zhou ◽  
Yu-chao Shang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Fear Extinction ◽  
Male Rats ◽  
Neonatal Rats ◽  
Stress Exposure ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Acid Type ◽  
Cation Chloride Cotransporters ◽  
The Brain

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

scholarly journals Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear-extinction Deficit

2021 ◽  
Author(s):  
Ben-zhen Chen ◽  
Li-hua Jiang ◽  
Ming-qiang Zhang ◽  
Ling Tan ◽  
Wen-qin Zhou ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Fear Extinction ◽  
Male Rats ◽  
Neonatal Rats ◽  
Stress Exposure ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Acid Type ◽  
Cation Chloride Cotransporters ◽  
The Brain

Abstract Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 hours on postnatal days (P) 5, 6, 7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, 26, 27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear-extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

scholarly journals Regular Music Exposure in Juvenile Rats Facilitates Conditioned Fear Extinction and Reduces Anxiety after Foot Shock in Adulthood

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Si Chen ◽  
Tuo Liang ◽  
Fiona H. Zhou ◽  
Ye Cao ◽  
Chao Wang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Conditioning Session ◽  
Fear Extinction ◽  
Extinction Training ◽  
Anterior Cingulate ◽  
Stressful Event ◽  
Sprague Dawley ◽  
Positive Role ◽  
Juvenile Rats

Music exposure is known to play a positive role in learning and memory and can be a complementary treatment for anxiety and fear. However, whether juvenile music exposure affects adult behavior is not known. Two-week-old Sprague-Dawley rats were exposed to music for 2 hours daily or to background noise (controls) for a period of 3 weeks. At 60 days of age, rats were subjected to auditory fear conditioning, fear extinction training, and anxiety-like behavior assessments or to anterior cingulate cortex (ACC) brain-derived neurotrophic factor (BDNF) assays. We found that the music-exposed rats showed significantly less freezing behaviors during fear extinction training and spent more time in the open arm of the elevated plus maze after fear conditioning when compared with the control rats. Moreover, the BDNF levels in the ACC in the music group were significantly higher than those of the controls with the fear conditioning session. This result suggests that music exposure in juvenile rats decreases anxiety-like behaviors, facilitates fear extinction, and increases BDNF levels in the ACC in adulthood after a stressful event.

scholarly journals Pharmacokinetics of α-Pyrrolidinovalerophenone in Male Rats with and without Vaccination with an α-Pyrrolidinovalerophenone Vaccine

2021 ◽  
Vol 24 ◽  
pp. 267-276
Author(s):  
Samantha McClenahan ◽  
Melinda Gunnell ◽  
Michael Owens
Keyword(s):  
Treatment Time ◽  
Area Under The Curve ◽  
Early Time ◽  
Volume Of Distribution ◽  
Male Rats ◽  
Serum Concentrations ◽  
Sprague Dawley ◽  
Serum Samples ◽  
Maximum Serum ◽  
The Brain

PURPOSE: α-Pyrrolidinovalerophenone (α-PVP) is a second-generation synthetic cathinone which acts as an inhibitor at the dopamine and norepinephrine transporters in the brain. These novel studies determined the pharmacokinetics (PK) of α-PVP in rats and then evaluated the effects of an α-PVP vaccine on the PK profile. METHODS: Adult male Sprague-Dawley rats were randomly divided into treatment groups (n = 24/group) in which the vaccinated rats received an initial and two booster immunizations of the α-PVP vaccine at 0, 3, and 9 wks. Control rats received saline injections. α-PVP (0.56, 1, 3 mg/kg, sc) was then administered to both groups between 11-12 weeks and serum samples were collected for determination of α-PVP serum concentrations by LC-MS/MS (n=6 rats/treatment/time). At 13 weeks, brain, heart and kidney concentrations of α-PVP were determined by LC-MS/MS after administration of 1 mg/kg α-PVP (n=4-5 rats/treatment/time). RESULTS: PK values in control rats showed dose-dependent increases in maximum serum concentrations (Cmax) and area under the curve (AUCinf) values with an elimination half-life (t1/2) of approximately 2.1 h. α-PVP exhibited linear PK profile in control rats. Vaccinated rats had significantly (p<0.05) higher serum Cmax and AUCinf values than controls, and significantly reduced total body clearance, volume of distribution and t1/2 values. Vaccinated rats had significantly lower α-PVP concentrations in the brain, heart, and kidney in comparison to control rats at early time points. CONCLUSION: Vaccination with the novel α-PVP vaccine significantly altered serum PK leading to a time-dependent reduction in brain, kidney and heart concentrations of α-PVP compared to controls.

Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

Heterotransplantation of malignant human gliomas in neonatal rats

1988 ◽  
Vol 69 (6) ◽  
pp. 928-933 ◽  
Author(s):  
Rafael J. Tamargo ◽  
Jonathan I. Epstein ◽  
Henry Brem
Keyword(s):  
Human Glioma ◽  
Neonatal Rats ◽  
Sprague Dawley ◽  
Human Gliomas ◽  
Newborn Rat ◽  
Content Type ◽  
Sprague Dawley Rats ◽  
Heterologous Transplantation ◽  
Subcutaneous Space ◽  
The Brain

✓ Three human glioma cell lines (TE-671 medulloblastoma, U-87 MG glioblastoma, and U-373 MG glioblastoma) were transplanted to the quadrigeminal cistern of the brain in 37 newborn Sprague-Dawley rats and to the subcutaneous space in 30 of their siblings. Two of the three gliomas (the TE-671 medulloblastoma and the U-87 MG glioblastoma) grew both intracranially and subcutaneously. The U-373 MG glioblastoma did not grow in either site. The resulting tumors expressed unique morphological features characteristic of their tissue of origin. The newborn rat represents a model for the heterologous transplantation of human gliomas, providing a biological window for the study of these lesions.

scholarly journals Sites and sources of sympathoexcitation in obese male rats: role of brain insulin

2020 ◽  
Vol 318 (3) ◽  
pp. R634-R648 ◽  
Author(s):  
Zhigang Shi ◽  
Ding Zhao ◽  
Priscila A. Cassaglia ◽  
Virginia L. Brooks
Keyword(s):  
Insulin Receptors ◽  
Male Rats ◽  
Melanocortin Receptor ◽  
Sprague Dawley ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Y1 Receptors ◽  
The Brain ◽  
Obese Male

In males, obesity increases sympathetic nerve activity (SNA), but the mechanisms are unclear. Here, we investigate insulin, via an action in the arcuate nucleus (ArcN), and downstream neuropathways, including melanocortin receptor 3/4 (MC3/4R) in the hypothalamic paraventricular nucleus (PVN) and dorsal medial hypothalamus (DMH). We studied conscious and α-chloralose-anesthetized Sprague-Dawley rats fed a high-fat diet, which causes obesity prone (OP) rats to accrue excess fat and obesity-resistant (OR) rats to maintain fat content, similar to rats fed a standard control (CON) diet. Nonspecific blockade of the ArcN with muscimol and specific blockade of ArcN insulin receptors (InsR) decreased lumbar SNA (LSNA), heart rate (HR), and mean arterial pressure (MAP) in OP, but not OR or CON, rats, indicating that insulin supports LSNA in obese males. In conscious rats, intracerebroventricular infusion of insulin increased MAP only in OP rats and also improved HR baroreflex function from subnormal to supranormal. The brain sensitization to insulin may elucidate how insulin can drive central SNA pathways when transport of insulin across the blood-brain barrier may be impaired. Blockade of PVN, but not DMH, MC3/4R with SHU9119 decreased LSNA, HR, and, MAP in OP, but not OR or CON, rats. Interestingly, nanoinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased LSNA only in OP rats, similar to PVN MTII-induced increases in LSNA in CON rats after blockade of sympathoinhibitory neuropeptide Y Y1 receptors. ArcN InsR expression was not increased in OP rats. Collectively, these data indicate that obesity increases SNA, in part via increased InsR signaling and downstream PVN MC3/4R.

Abstract WMP116: The Effects of Immediate Treatment with Inter-alpha Inhibitor Proteins on Apoptosis in Neonatal Rats Exposed to Hypoxic-ischemic Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Sakura Nakada ◽  
Xiaodi Chen ◽  
Yow-Pin Lim ◽  
Barbara S Stonestreet
Keyword(s):  
Sham Group ◽  
Systemic Treatment ◽  
Male Rats ◽  
Neonatal Rats ◽  
Artery Ligation ◽  
Neuroprotective Effects ◽  
Group Assignment ◽  
Carotid Artery Ligation ◽  
Cellular Markers ◽  
The Brain

Background: Hypoxia-Ischemia (HI) is a condition in which the brain is deprived of adequate blood and oxygen supplies, resulting in a variety of neurodevelopmental morbidities in newborns. Inter-Alpha Inhibitor Proteins (IAIPs) are immunomodulatory proteins that have anti-inflammatory properties in systemic inflammatory disorders. The neuroprotective effects of treatment with IAIPs on apoptosis resulting from HI-related injury have not been examined yet. Objective: To investigate the effects of systemic treatment with IAIPs on apoptosis in HI-exposed neonatal rats. Design/Methods: Postnatal day 7 rats were randomly assigned to one of three groups: Placebo-Sham (PL-Sham, n=8), Placebo-HI (PL-HI, n=8) and IAIP-HI (n=8) groups. The PL-Sham group was not exposed to HI and received placebo intraperitoneally (0.9% NaCl); the PL-HI group was exposed to HI and received placebo (0.9% NaCl); the IAIP-HI group was exposed to HI and received IAIPs treatment (30 mg/kg). The Rice-Vannucci model was utilized to induce HI-related brain injury: unilateral carotid artery ligation followed by hypoxia (90 min in 8% O 2 ). Rat sex was recorded. Placebo or IAIP treatment was given at 0, 24 and 48 hours after HI, and brains were perfused and fixed at 72 hours. Fixed brain tissues were immunohistochemically stained with TUNEL apoptotic cellular markers. Apoptotic cells were counted without knowledge of the group assignment using the StereoInvestigator 10.0, Fractionator probe (MBF Bioscience). Results: There were more TUNEL positive cells in the PL-HI group than in the PL-Sham group overall (female+male) as well as in males in the cortex, total hemisphere and hippocampus (all P <0.05), but not in females ( P =0.11, P =0.30 and P =0.12, respectively). There appeared to be less apoptosis in the male IAIP-treated HI rats compared with the male placebo-treated HI rats ( P =0.29 for hemisphere and cortex, P =0.51 for hippocampus). Conclusion: Apoptosis is significantly increased after HI in the total hemisphere, cortex, and hippocampus of male neonatal rats, but not in females. Further investigation is needed to determine the neuroprotective effects of IAIPs on apoptosis in HI-exposed neonatal rats, although preliminary data suggests a protective trend for male rats.

scholarly journals The role of carbonic anhydrases in extinction of contextual fear memory

2020 ◽  
Vol 117 (27) ◽  
pp. 16000-16008 ◽  
Author(s):  
Scheila Daiane Schmidt ◽  
Alessia Costa ◽  
Barbara Rani ◽  
Eduarda Godfried Nachtigall ◽  
Maria Beatrice Passani ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Fear Conditioning ◽  
Fear Extinction ◽  
Systemic Administration ◽  
Contextual Fear Conditioning ◽  
Ventromedial Prefrontal Cortex ◽  
Carbonic Anhydrases ◽  
Contextual Fear ◽  
Extinction Memory ◽  
The Brain

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in mammals with 16 isoforms that differ in terms of catalytic activity as well as cellular and tissue distribution. CAs catalyze the conversion of CO2to bicarbonate and protons and are involved in various physiological processes, including learning and memory. Here we report that the integrity of CA activity in the brain is necessary for the consolidation of fear extinction memory. We found that systemic administration of acetazolamide, a CA inhibitor, immediately after the extinction session dose-dependently impaired the consolidation of fear extinction memory of rats trained in contextual fear conditioning.d-phenylalanine, a CA activator, displayed an opposite action, whereas C18, a membrane-impermeable CA inhibitor that is unable to reach the brain tissue, had no effect. Simultaneous administration of acetazolamide fully prevented the procognitive effects ofd-phenylalanine. Whereasd-phenylalanine potentiated extinction, acetazolamide impaired extinction also when infused locally into the ventromedial prefrontal cortex, basolateral amygdala, or hippocampal CA1 region. No effects were observed when acetazolamide ord-phenylalanine was infused locally into the substantia nigra pars compacta. Moreover, systemic administration of acetazolamide immediately after the extinction training session modulated c-Fos expression on a retention test in the ventromedial prefrontal cortex of rats trained in contextual fear conditioning. These findings reveal that the engagement of CAs in some brain regions is essential for providing the brain with the resilience necessary to ensure the consolidation of extinction of emotionally salient events.

Sign in / Sign up

Export Citation Format

Share Document