Serotonin depletion reduces both acquisition and expression of context-conditioned fear

2021 ◽  
pp. 1-8
Author(s):  
S. Melker Hagsäter ◽  
Robert Pettersson ◽  
Axel Holmäng ◽  
Elias Eriksson
Keyword(s):  
Unconditioned Stimulus ◽  
Memory Consolidation ◽  
Clinical Studies ◽  
Conditioned Fear ◽  
Sprague Dawley ◽  
Serotonin Synthesis ◽  
Synthesis Inhibitor ◽  
Serotonin Depletion ◽  
Sprague Dawley Rats ◽  
The Impact

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.

scholarly journals Bed nuclei of the stria terminalis modulate memory consolidation via glucocorticoid-dependent and -independent circuits

2020 ◽  
Vol 117 (14) ◽  
pp. 8104-8114 ◽  
Author(s):  
Ryan T. Lingg ◽  
Shane B. Johnson ◽  
Eric B. Emmons ◽  
Rachel M. Anderson ◽  
Sara A. Romig-Martin ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Avoidance Training ◽  
Stress Hormones ◽  
Inhibitory Avoidance ◽  
Stria Terminalis ◽  
Sprague Dawley ◽  
Synthesis Inhibitor ◽  
Memory Enhancement ◽  
Sprague Dawley Rats ◽  
Corticosterone Response

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary–adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation—but not inhibition—of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.

scholarly journals Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Catherine Crinigan ◽  
Matthew Calhoun ◽  
Karen L. Sweazea
Keyword(s):  
Kidney Disease ◽  
Renal Mass ◽  
Early Stage ◽  
Young Male ◽  
Protective Effects ◽  
Sprague Dawley ◽  
High Fat ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
The Impact

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

2018 ◽  
Vol 31 (1) ◽  
pp. 46-51
Author(s):  
S. Melker Hagsäter ◽  
Johan Thorén ◽  
Robert Pettersson ◽  
Elias Eriksson
Keyword(s):  
Unconditioned Stimulus ◽  
Serotonin Reuptake ◽  
Conditioned Response ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Conditioned Fear ◽  
Noise Burst ◽  
Selective Serotonin ◽  
Unconditioned Response ◽  
Acute Administration ◽  
Sprague Dawley

AbstractObjectiveWhereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.MethodsMale Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.ResultsNoise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.ConclusionThe data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.

scholarly journals Structural Alteration in Dermal Vessels and Collagen Bundles following Exposure of Skin Wound to Zeolite–Bentonite Compound

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Shahram Paydar ◽  
Ali Noorafshan ◽  
Behnam Dalfardi ◽  
Shahram Jahanabadi ◽  
Seyed Mohammad Javad Mortazavi ◽  
...  
Keyword(s):  
Healing Process ◽  
Volume Density ◽  
Skin Wound ◽  
Sprague Dawley ◽  
Small Vessels ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Sterile Normal Saline ◽  
Animal Skin ◽  
The Impact

Background. This study examines the impact of one-time direct application of haemostatic agent zeolite–bentonite powder to wounded skin on the healing process in rats. Materials and Methods. 24 male Sprague-Dawley rats were randomly allocated into two groups (n=12): (1) the rats whose wounds were washed only with sterile normal saline (NS-treated) and (2) those treated with zeolite–bentonite compound (ZEO-treated). The wound was circular, full-thickness, and 2 cm in diameter. At the end of the 12th day, six animals from each group were randomly selected and terminated. The remaining rats were terminated after 21 days. Just after scarification, skin samples were excised and sent for stereological evaluation. Results. The results showed a significant difference between the two groups regarding the length density of the blood vessels and diameter of the large and small vessels on the 12th day after the wound was inflicted. Besides, volume density of both the dermis and collagen bundles was reduced by 25% in the ZEO-treated rats in comparison to the NS-treated animals after 21 days. Conclusions. One-time topical usage of zeolite–bentonite haemostatic powder on an animal skin wound might negatively affect the healing process through vasoconstriction and inhibition of neoangiogenesis.

scholarly journals Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats

2016 ◽  
Vol 310 (2) ◽  
pp. R115-R124 ◽  
Author(s):  
Kathryn R. Walsh ◽  
Jill T. Kuwabara ◽  
Joon W. Shim ◽  
Richard D. Wainford
Keyword(s):  
Blood Pressure ◽  
Sodium Chloride ◽  
Salt Sensitivity ◽  
Dietary Sodium ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sodium Chloride Cotransporter ◽  
Sprague Dawley Rats ◽  
Salt Sensitive Hypertension ◽  
The Impact

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.

scholarly journals The Impact of DJOS Surgery, a High Fat Diet and a Control Diet on the Enzymes of Glucose Metabolism in the Liver and Muscles of Sprague-Dawley Rats

2019 ◽  
Vol 10 ◽  
Author(s):  
Dominika Stygar ◽  
Dorian Andrare ◽  
Barbara Bażanów ◽  
Elżbieta Chełmecka ◽  
Tomasz Sawczyn ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
Control Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
The Impact

scholarly journals Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 1007 ◽  
Author(s):  
Jessica C. Gaspar ◽  
Bright N. Okine ◽  
Alvaro Llorente-Berzal ◽  
Michelle Roche ◽  
David P. Finn
Keyword(s):  
Conditioned Fear ◽  
Intraperitoneal Administration ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Intraplantar Injection ◽  
Conditioned Analgesia ◽  
Sprague Dawley Rats ◽  
Pharmacological Blockade ◽  
Peroxisome Proliferator Activated Receptors ◽  
Nociceptive Behaviour

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPARα, PPARβ/δ, PPARγ) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPARα (GW6471), PPARβ/δ (GSK0660) or PPARγ (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPARα and PPARβ/δ antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPARγ antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPARα and PPARβ/δ in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPARγ potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone.

scholarly journals Effects of Diet-Induced Obesity and Deficient in Vitamin D on Spermatozoa Function and DNA Integrity in Sprague-Dawley Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
O. Merino ◽  
R. Sánchez ◽  
B. M. Gregorio ◽  
F. J. Sampaio ◽  
J. Risopatrón
Keyword(s):  
Vitamin D ◽  
Dna Fragmentation ◽  
High Fat Diet ◽  
Control Diet ◽  
Sperm Function ◽  
Sprague Dawley ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
The Impact

Obesity has adverse effects on male fertility and usually is diagnosed with a prevalence of vitamin D deficiency (VD-). Discussion on the impact of obesity/VD- on sperm function has been limited. This study analyzed the effects of diet-induced obesity/VD- on viability and plasma membrane integrity (PMI), superoxide anion (O2-) level, and DNA fragmentation (DNAfrag) in sperm Sprague-Dawley rats. The males were randomized into four groups and fed for a period of 12 weeks: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+), and G4: high-fat diet without vitamin D (HF/VD-). Sperm function parameters were analyzed by flow cytometry. PMI percentages and O2- levels were not affected by any of the diets. DNA fragmentation was increasing significantly (p<0.05) in the spermatozoa of animals with diets vitamin D deficient (G2) and diet-induced obesity (G4). Our results allow us to point out that diet-induced obesity and VD- produce greater damage in DNA sperm of rats. The use of nutraceuticals containing vitamin D could be reducing the risk of fragmentation of DNA in spermatozoa.

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