scholarly journals Lack of drug-induced post-retrieval amnesia for auditory fear memories in rats

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Laura Luyten ◽  
Anna Elisabeth Schnell ◽  
Natalie Schroyens ◽  
Tom Beckers

Abstract Background Long-term memory formation is generally assumed to involve the permanent storage of recently acquired memories, making them relatively insensitive to disruption, a process referred to as memory consolidation. However, when 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 by pharmacologically interfering with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol). Here, we find that, contrary to expectations, systemic pharmacological manipulations in auditory fear-conditioned rats do not lead to drug-induced post-retrieval amnesia. Results 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). Conclusions In contrast with previously 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.

2020 ◽  
Author(s):  
Laura Luyten ◽  
Anna Elisabeth Schnell ◽  
Natalie Schroyens ◽  
Tom Beckers

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


2017 ◽  
Vol 36 (12) ◽  
pp. 1295-1302 ◽  
Author(s):  
L Liang ◽  
Z Ma ◽  
M Dong ◽  
J Ma ◽  
A Jiang ◽  
...  

Postoperative cognitive dysfunction, which is associated with a wide range of cognitive functions including working memory, long-term memory, information processing, attention, and cognitive flexibility, is a major clinical issue in geriatric surgical patients. The aim of the current study was to determine the protective role and possible mechanisms of salidroside against isoflurane-induced cognitive impairment. Sprague Dawley rats were randomly assigned to five groups and were treated with or without salidroside before isoflurane exposure. Open-field and fear conditioning tests were conducted to evaluate the cognitive function of the rats. Moreover, the hippocampus tissues were obtained for biochemical analysis. The results showed that the isoflurane anesthesia decreased the freezing time to context significantly at 48 h after the isoflurane exposure in the fear conditioning test. Salidroside could ameliorate isoflurane-induced cognitive dysfunction. Further analysis demonstrated salidroside markedly suppressed the release of tumor necrosis factor-α and interleukin-1β. Moreover, salidroside reversed the decreased activity of choline acetyltransferase, superoxide dismutase, glutathione peroxidase, and content of acetylcholine, as well as the increased activity of acetylcholine esterase and content of malondialdehyde in hippocampal tissue of isoflurane-exposed rats. According to the results, we concluded that that salidroside has a protective effect against isoflurane-induced cognitive dysfunction by inhibiting excessive inflammatory responses, decreasing oxidative stress, and regulating the cholinergic system.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Smitha Karunakaran

AbstractIn this study we demonstrate that 2 month old APPswe/PS1dE9 mice, a transgenic model of Alzheimer’s disease, exhibited intact short-term memory in Pavlovian hippocampal—dependent contextual fear learning task. However, their long-term memory was impaired. Intra-CA1 infusion of isoproterenol hydrochloride, the β-adrenoceptor agonist, to the ventral hippocampus of APPswe/PS1dE9 mice immediately before fear conditioning restored long-term contextual fear memory. Infusion of the β-adrenoceptor agonist + 2.5 h after fear conditioning only partially rescued the fear memory, whereas infusion at + 12 h post conditioning did not interfere with long-term memory persistence in this mouse model. Furthermore, Intra-CA1 infusion of propranolol, the β-adrenoceptor antagonist, administered immediately before conditioning to their wildtype counterpart impaired long-term fear memory, while it was ineffective when administered + 4 h and + 12 h post conditioning. Our results indicate that, long-term fear memory persistence is determined by a unique β-adrenoceptor sensitive time window between 0 and + 2.5 h upon learning acquisition, in the ventral hippocampal CA1 of APPswe/PS1dE9 mice. On the contrary, β-adrenoceptor agonist delivery to ventral hippocampal CA1 per se did not enhance innate anxiety behaviour in open field test. Thus we conclude that, activation of learning dependent early β-adrenoceptor modulation underlies and is necessary to promote long-term fear memory persistence in APPswe/PS1dE9.


Author(s):  
Magdalena Białoń ◽  
Agnieszka Chocyk ◽  
Iwona Majcher-Maślanka ◽  
Marcelina Żarnowska ◽  
Krzysztof Michalski ◽  
...  

Abstract Background The aim of the present study was to evaluate the effect of 1MeTIQ on fear memory and social interaction in an MK-801-induced model of schizophrenia. The results obtained after administration of 1MeTIQ were compared with those obtained with olanzapine, an antipsychotic drug. Methods Sprague–Dawley rats received a single injection of MK-801 to induce behavioral disorders. 1MeTIQ was given either acutely in a single dose or chronically for 7 consecutive days. Olanzapine was administered once. In groups receiving combined treatments, 1MeTIQ or olanzapine was administered 20 min before MK-801 injection. Contextual fear conditioning was used to assess disturbances in fear memory (FM), and the sociability of the rats was measured in the social interaction test (SIT). Biochemical analysis was carried out to evaluate monoamine levels in selected brain structures after treatment. Results Our results are focused mainly on data obtained from neurochemical studies, demonstrating that 1MeTIQ inhibited the MK-801-induced reduction in dopamine levels in the frontal cortex and increased the 5-HT concentration. The behavioral tests revealed that acute administration of MK-801 caused disturbances in both the FM and SIT tests, while neither 1MeTIQ nor olanzapine reversed these deficits. Conclusion 1MeTIQ, although pharmacologically effective (i.e., it reverses MK-801-induced changes in monoamine activity), did not influence MK-801-induced social and cognitive deficits. Thus, our FM tests and SIT did not support the main pharmacological hypotheses that focus on dopamine system stabilization and dopamine–serotonin system interactions as probable mechanisms for inhibiting the negative symptoms of schizophrenia.


Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

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.


2020 ◽  
Vol 6 (1) ◽  
pp. 584-600
Author(s):  
Amaal Al-Gamde ◽  
Thora Tenbrink

AbstractThis study explores the influence of a government’s ideology on linguistic representation in a news agency that characterizes itself as independent. It focuses on the coverage of the Syrian civil war as reported by the Iranian news agency Fars, addressing the discursive constructions of anti-government powers in relevant online reports released between 2013 and 2015. Since the Islamic Republic of Iran was a major regional ally of the Syrian government, we questioned the extent to which ideological independence could be expected during a politically critical time frame. Taking a corpus-based linguistic approach, the study explores the semantic macrostructures representing the opposition as well as the lexical clusters and keywords characterizing the news discourse. The findings indicate that Fars’ representation of the Syrian Revolution was, to some extent, biased, despite its claimed independence of the government’s political stance. It excluded the Sunni social actors, suppressed the Islamic faction identity of the rebels and depicted the uprising as a war against foreign-backed militants. The rebels were stereotyped in terms of terrorism and non-Syrians. In addition, the analysis reveals Fars’ tendency to emphasize the power of the government, depicting it as the defender of the Arab land and foregrounding the discourse of international conspiracy against Syria. The results of this work project the dimension of media bias caused by the underpinning political perspective of media institutions.


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