scholarly journals Parametric modulators of sex-biased conditioned fear responding

2021 ◽  
Author(s):  
Julia R Mitchell ◽  
Sean G Trettel ◽  
Anna J Li ◽  
Sierra Wasielewski ◽  
Kylie A Huckleberry ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Early Recognition ◽  
Conditioned Fear ◽  
Sprague Dawley ◽  
Multiple Dimensions ◽  
Sprague Dawley Rats ◽  
Experimental Parameters ◽  
Behavioral Paradigm ◽  
Data Files ◽  
Chamber Size

Pavlovian fear conditioning is a widely used behavioral paradigm for studying associative learning in rodents. Despite early recognition that subjects may engage in a variety of behaviors that reflect the experimental parameters of a given protocol, the last several decades have seen the field narrow its focus to measure freezing as the sole indicator of conditioned fear. Additionally, unconditioned responses such as shock-related activity are rarely considered. We previously reported that female Sprague Dawley rats are more likely than males to engage in darting, an escape-like conditioned response that is associated with heightened shock reactivity, but we did not establish whether darting was sensitive to manipulations of factors such as chamber size, shock intensity, or number of trials. Our goal here was to address these questions by defining parametric and phenotypic predictors of darting in both sexes. To better capture fear-related behavioral repertoires in our animals, we developed ScaredyRat, a custom Python tool that analyzes Noldus Ethovision-generated raw data files to identify Darters and quantify both conditioned and unconditioned responses. We find that like freezing, darting probability scales with experimental alterations in multiple dimensions. In most cases, the sex bias towards females persists, but males will transition to darting in extended, or overtraining fear conditioning protocols.

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 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 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 Rats remember: Lack of drug-induced post-retrieval amnesia for auditory fear memories

2020 ◽  
Author(s):  
Laura Luyten ◽  
Anna Elisabeth Schnell ◽  
Natalie Schroyens ◽  
Tom Beckers
Keyword(s):  
Fear Conditioning ◽  
Critical Time ◽  
Fear Memory ◽  
Time Frame ◽  
List Type ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Administration Routes ◽  
Sprague Dawley Rats

AbstractWhen retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example through pharmacological interference with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol).In a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20-40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide) and consolidation of extinction memories (cycloheximide).Thus, in contrast with most published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.HighlightsWe aimed to replicate post-retrieval amnesia for auditory fear memories in ratsWe performed a series of well-powered pharmacological interference experimentsPropranolol, rapamycin, anisomycin or cycloheximide was injected upon retrievalBayesian stats found substantial evidence for the absence of post-retrieval amnesiaThe effect is less reproducible and generalizable than what the literature suggests

Strain differences in coping behaviour, novelty seeking behaviour, and susceptibility to socially conditioned fear: A comparison between Wistar and Sprague Dawley rats

Stress ◽  
2009 ◽  
Vol 12 (6) ◽  
pp. 507-516 ◽  
Author(s):  
Frederick R. Walker ◽  
Sundresan Naicker ◽  
Madeleine Hinwood ◽  
Nicole Dunn ◽  
Trevor A. Day
Keyword(s):  
Conditioned Fear ◽  
Strain Differences ◽  
Novelty Seeking ◽  
Sprague Dawley ◽  
Coping Behaviour ◽  
Sprague Dawley Rats

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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