Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder

Morena, Maria; Berardi, Andrea; Peloso, Andréa; Valeri, Daniela; Palmery, Maura; Trezza, Viviana; Schelling, Gustav; Campolongo, Patrizia

doi:10.1016/j.bbr.2017.04.048

Cited by 45 publications

(28 citation statements)

References 43 publications

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“…Most preventive measures that have been explored fall into the category of “early intervention”, in which treatment is given after the traumatic event, but prior to development of related symptoms (reviewed in Birur et al, 2017 ). Prophylactic oxytocin may offer the same neuroprotective benefits of other treatments (Vaiva et al, 2003 ; Baker et al, 2009 ; Daskalakis et al, 2013 ; Morena et al, 2017 ) without the risks associated with long-term treatment (Baker et al, 2009 ). Remedial treatment after a traumatic event might be most practical, as the majority of traumatic events cannot be predicted; however, if prophylactic or contemporaneous treatments offer significant protection, these treatments could be beneficial in settings such as combat warfare, law enforcement operations and preoperative care.…”

Section: Discussionmentioning

confidence: 99%

Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

Renicker

Cysewski

Palmer

et al. 2018

Front. Behav. Neurosci.

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Oxytocin treatment reduces signs of long-term emotional stress after exposure to trauma; however, little is known about the potential protective effects of oxytocin treatment on behavioral and physiological changes associated with extreme stress exposure. The objective of this study was to investigate oxytocin treatment as a prophylactic measure against rat signs of fear. Two separate experiments were conducted in which the time of intranasal oxytocin administration differed. Intranasal oxytocin (1.0 μg/kg) was administered 5 min after daily exposure to foot shock in Experiment #1 and 1 h before foot shock in Experiment #2. In Experiment #1, possible massage-evoked oxytocin release (5 min after foot shock) was also investigated. In both experiments, a contextual fear conditioning procedure was employed in which stress was induced via inescapable foot shock (3 days, 40 shocks/day, 8 mA/shock) in a fear conditioning chamber. Male Sprague-Dawley rats (n = 24) were divided into four groups (n = 6, per group) for each experiment. Experiment #1 groups: Control Exp#1 (intranasal saline and no foot shock); Stress Exp#1 (intranasal saline 5 min after foot shock); Massage+Stress Exp#1 (massage-like stroking and intranasal saline 5 min after foot shock); Oxytocin+Stress Exp#1 (intranasal oxytocin 5 min after foot shock). Experiment #2 groups: Control Exp#2 (intranasal saline and no foot shock); Stress Exp#2 (intranasal saline 1 h before foot shock); Oxytocin Exp#2 (intranasal oxytocin and no foot shock); Oxytocin+Stress Exp#2 (intranasal oxytocin 1 h before foot shock). One week after fear conditioning (and other treatments), rats were independently evaluated for behavioral signs of fear. Two weeks after conditioning, physiological signs of fear were also assessed (Experiment #1). Relative to controls, rats treated with intranasal oxytocin 5 min after daily foot shock sessions exhibited significantly less immobility upon re-exposure to the shock chamber and attenuated physiological responses related to fear (e.g., elevated heart rate and blood pressure). Furthermore, intranasal oxytocin treatment given 1 h before daily foot shock sessions significantly decreased immobility and defecation upon re-exposure to the shock chamber, relative to controls. The results of this study suggest that prophylactic intranasal oxytocin, administered contemporaneously with aversive stimuli, mitigates behavioral and physiological responses associated with traumatic stress.

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Section: Discussionmentioning

confidence: 99%

Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

Renicker

Cysewski

Palmer

et al. 2018

Front. Behav. Neurosci.

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“…92,93 In some cases, different anaesthetics can cause the opposite effect on the same task: for example, dexmedetomidine may impair retrieval in a certain task, while ketamine enhances it. 94 These studies suggest that stimulus reception, integration, and storage are possible under anaesthesia, which could have relevant translational implications. In the next sections we explore conditions under which such learning occurs.…”

Section: Implicit Fear Memory Under General Anaesthesiamentioning

confidence: 96%

“…72,108 Propofol given at a low dose during the consolidation window after FeC can enhance retrieval. 94,109 Midazolam enhances both retrieval and acquisition at low doses. 110 All of these studies were performed using a single dose, never reaching unconsciousness (or loss of righting reflex), and can be regarded as equivalent to the induction limb of the anaesthesia hysteresis curve.…”

Section: Low Doses Of Anaesthetics Can Enhance Fear Memorymentioning

confidence: 99%

“…High dose ketamine (but not low dose ketamine) and low dose propofol enhance retrieval, while dexmedetomidine decreases retrieval when given in a consolidation window. 63,69,94,109 It appears that formation and consolidation of traumatic implicit memories are influenced not only during the exposure itself (e.g. during surgery), but also by the state of the subject before and after the exposure, and even after a repeated exposure to the environment (reactivation).…”

Section: Anaesthetics Timing and Conditioningmentioning

confidence: 99%

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Implicit aversive memory under anaesthesia in animal models: a narrative review

Samuel

Taub

Paz

et al. 2018

British Journal of Anaesthesia

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Explicit memory after anaesthesia has gained considerable attention because of its negative implications, while implicit memory, which is more elusive and lacks patients' explicit recall, has received less attention and dedicated research. This is despite the likely impact of implicit memory on postoperative long-term well-being and behaviour. Given the scarcity of human data, fear conditioning in animals offers a reliable model of implicit learning, and importantly, one where we already have a good understanding of the underlying neural circuitry in awake conditions. Animal studies provide evidence that fear conditioning occurs under anaesthesia. The effects of different anaesthetics on memory are complex, with different drugs interacting at different stages of learning. Modulatory suppressive effects can be because of context, specific drugs, and dose dependency. In some cases, low doses of general anaesthetics can actually lead to a paradoxical opposite effect. The underlying mechanisms involve several neurotransmitter systems, acting mainly in the amygdala, hippocampus, and neocortex. Here, we review animal studies of aversive conditioning under anaesthesia, discuss the complex picture that arises, identify the gaps in knowledge that require further investigation, and highlight the potential translational relevance of the models.

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“…The lack of ketamine effects on the ETM rats performance, acutely or 24 h after its administration, reinforces the controversial findings reported in previous studies, as described in table 1. For example, anesthetic doses of ketamine induced anxiolytic-like (Hayase et al, 2006), anxiogenic-like (Morena et al, 2017) or no effect (Magalhaes et al, 2017) in different tests of anxiety. Regarding sub-anesthetic doses of ketamine, similar mix of outcomes has been previously reported (as detailed in Table 1).…”

Section: New Findingsmentioning

confidence: 99%

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

Silote

Oliveira

Ribeiro

et al. 2019

Preprint

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Highlights  Ketamine induces mixed effects in animal anxiety tests  Few studies investigated the individual effects of S-ketamine in anxiety/fear tests  None study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors  Systemic ketamine does not affect panic-like behaviors in the elevated T-maze Abstract Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies.Regarding ketamine effects on anxiety, there is a widespread discordance among preclinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species.Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.

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Effects of ketamine, dexmedetomidine and propofol anesthesia on emotional memory consolidation in rats: Consequences for the development of post-traumatic stress disorder

Cited by 45 publications

References 43 publications

Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

Implicit aversive memory under anaesthesia in animal models: a narrative review

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

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