Amnestic Agent Research Articles

The translational inhibitor and amnestic agent emetine also suppresses ongoing hippocampal neural activity similarly to other blockers of protein synthesis.

The consolidation of memory is thought to ultimately depend on the synthesis of new proteins, since translational inhibitors such as anisomycin and cycloheximide adversely affect the permanence of long-term memory. However, when applied directly in brain, these agents also profoundly suppress neural activity to an extent that is directly correlated to the degree of protein synthesis inhibition caused. Given that neural activity itself is likely to help mediate consolidation, this finding is a serious criticism of the strict de novo protein hypothesis of memory. Here, we test the neurophysiological effects of another translational inhibitor, emetine. Unilateral intra-hippocampal infusion of emetine suppressed ongoing local field and multiunit activity at ipsilateral sites as compared to the contralateral hippocampus in a fashion that was positively correlated to the degree of protein synthesis inhibition as confirmed by autoradiography. This suppression of activity was also specific to the circumscribed brain region in which protein synthesis inhibition took place. These experiments provide further evidence that ongoing protein synthesis is necessary and fundamental for neural function and suggest that the disruption of memory observed in behavioral experiments using translational inhibitors may be due, in large part, to neural suppression.

Low Dose Propofol at the End of Sevoflurane Anesthesia Reduces Emergence Agitation in Children: A Prospective Observational Study

Introduction: EA is characterized by agitation, inconsolable sobbing, disorientation, delusions, and hallucinations, decreased cognition and memory. Sevoflurane is widely used as an anesthetic agent for children because of its less pungent nature, lower solubility but it has a greater incidence of EA in preschool aged children. Propofol is a hypnotic amnestic agent with a short duration of action, commonly used for sedation, induction, and maintaining anesthesia and it has been used to prevent Emergence agitation. Aim of the Study: The aim of this study was to determine the efficacy of low dose propofol in reducing the incidence of EA at the end of face-mask sedation with sevoflurane. Methods: This was a prospective observational study and was conducted in the Department of Pediatric Anesthesia of Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh during the period from July, 2021 to December, 2021.In our study we took 220 children operated for hernia were randomized into two groups – Group A (Control group, n=110) and Group B (Propofol group, n= 110). Result: In total 220 patients from both the groups completed the study. In our study we found the mean age in group A & B was 6.3 ± 1.6 & 6.1 ± 1.9 years respectively. The mean PAED score was 14.41 ± 2.59 & 9.83 ± 3.51, the mean emergence time was 7.1 ± 2.0 & 13.4 ± 2.5, time in PACU was 44.5 ± 5.9 & 46.6 ± 7.6 mins in control & propofol group respectively. In contrast to the control group, no patient in the propofol group experienced EA beyond 15 or 20 minutes of emergence. Conclusion: In our study, we found that 0.5mg,/kg propofol was effective in preventing Emergence Agitation in children underwent herniotomy with caudal block and who’s sedation were maintained with sevoflurane.

Modulation of methamphetamine memory reconsolidation by neural projection from basolateral amygdala to nucleus accumbens.

Drug-associated conditioned cues promote subjects to recall drug reward memory, resulting in drug-seeking and reinstatement. A consolidated memory becomes unstable after recall, such that the amnestic agent can disrupt the memory during the reconsolidation stage, which implicates a potential therapeutic strategy for weakening maladaptive memories. The basolateral amygdala (BLA) involves the association of conditioned cues with reward and aversive valences and projects the information to the nucleus accumbens (NAc) that mediates reward-seeking. However, whether the BLA-NAc projection plays a role in drug-associated memory reactivation and reconsolidation is unknown. We used methamphetamine (MeAM) conditioned place preference (CPP) to investigate the role of BLA-NAc neural projection in the memory reconsolidation. Two weeks before CPP training, we infused adeno-associated virus (AAV) carrying the designer receptor exclusively activated by designer drugs (DREADD) or control constructs. We infused clozapine-N-oxide (CNO) after the recall test to manipulate the neural activity of BLA-NAc projections in mice. We found that after recall, DREADD-mediated inhibition of BLA neurons projecting to the NAc core blunted consolidated MeAM-associated memory. Inhibition of BLA glutamatergic nerve terminals in the NAc core 1 h after recall disrupted consolidated MeAM-associated memory. However, inhibiting this pathway after the time window of reconsolidation failed to affect memory. Furthermore, under the condition without memory retrieval, DREADD-mediated activation of BLA-NAc core projection was required for amnesic agents to disrupt consolidated MeAM-associated memory. Our findings provide evidence that the BLA-NAc pathway activity is involved in the post-retrieval processing of MeAM-associated memory in CPP.

Choice of Anesthesia for Orthopedic Surgery in Elderly and Senile Patients (Review)

Management of elderly and senile patients is a major challenge due to significant comorbidity, especially in surgery under general anesthesia.The aim of the review was to identify the optimal method of anesthesia for knee arthroplasty in elderly patients based on the available clinical and experimental studies.We searched PubMed, Medline, and Elibrary.ru databases for relevant sources. Out of more than 300 publications initially analyzed, 113 literature sources (dating from 1951 to 2021) were included in the review, of which 80 were published within the last five years (2016–2021). The inclusion criteria were high informative value and relevance, except for sources cited as historical references. Both randomized multicenter studies and individual case reports were included in the review. Exclusion criteria were low informative value, outdated and repetitive data.We reviewed the physiology of elderly and senile patients, various variants of anesthesia, the use of neuroaxial anesthesia and peripheral regional blocks, xenon-based general anesthesia, assessed the advantages and drawbacks of each method, and discussed the monitoring of the depth of anesthesia and the issues of inraoperative awareness during knee arthroplasty in elderly and senile patients.Conclusion. The choice of anesthesia for knee arthroplasty in elderly and senile patients should be based on the risks of decompensation of cardiovascular comorbidities and cognitive impairment. No known anesthetic method is ideal in terms of safety. The use of xenon as the main anesthetic seems promising due to its cardio- and neuroprotective properties. However, its use is limited due to relatively high cost. Therefore, the search for optimal (lower than recommended) inhalation concentrations may lead to expanding use of xenon in elderly and senile patients. At the same time, the use of lower concentrations of the drug is associated with the intraoperative awakening and the need for its combination with narcotic analgesics or amnestic agents, which may not be optimal. In addition, the protective effect of xenon retrograde amnesia against the stress of unintended intraoperative awakening has not been studied, and routine methods of monitoring the depth of hypnosis when using xenon often yield skewed measurement results inconsistent with the clinical manifestations of anesthesia.Therefore, there is a need for further studies concerning the retrograde amnesic effect of xenon and search for optimal methods of assessing the depth of hypnosis when using this gas to safely reduce its inhalation concentration.

Ethics of Amnestics and Analgesics: The Role of Memory in Mediating Pain and Harm

Analgesia and amnesia represent two complimentary pillars of anesthesia directed, respectively, at mitigating the experience of pain and the processes of encoding that experience into memory. These elements are typically combined in modern anesthetic techniques, but some circumstances exist – such as conscious sedation – in which the conditions of amnesia are satisfied while analgesia plays an auxiliary and often incomplete role. These activities reflect a widely held yet underrecognized belief in clinical practice that although pain experiences may be short-lived, their representation in memory and its subsequent effects on thought and emotion can have enduring consequences for patients. In this exploratory article, we delineate phenomenal and abstract ontological categories of pain experience; advance a claim that they are treated by analgesic and amnestic agents, respectively; and describe how each class of experience is uniquely able to bring about individual harm. Beginning with the question of how it can be permissible to allow any preventable experiences or memories of pain, we identify that both phenomenal and abstract pain manifest on a spectrum of severity, each with an enigmatic threshold – unique to circumstance and individual – that determines whether or not pain will translate into harm, and what permissions therefore surround its treatment. Ultimately, we find that there are compelling physiological reasons for the concurrent use of analgesics and amnestics when pain experience exceeds these thresholds, while the treatment of “sub-threshold” experience in either class is a purely ethical imperative to be balanced with considerations of the potential harms posed by the treatments themselves.

Lack of Effect of Propranolol on the Reconsolidation of Conditioned Fear Memory due to a Failure to Engage Memory Destabilisation

The prospect of exploiting memory reconsolidation to treat mental health disorders has received great research interest, particularly following demonstrations that the β-adrenergic receptor antagonist propranolol, which is safe for use in humans, can disrupt the reconsolidation of pavlovian conditioned fear memories. However, recent studies have failed to replicate the effects of propranolol on fear memory reconsolidation, and have questioned whether treatments based upon reconsolidation blockade would be robust enough for clinical translation. It remains possible, though, that studies reporting no effect of propranolol on memory reconsolidation could be due to a failure to engage the memory destabilisation process, which is necessary for the memory to become susceptible to disruption with amnestic agents. Demonstrating that memory destabilisation has not been engaged is challenging when only using behavioural measures, but there are molecular correlates of memory destabilisation that can be used to determine whether memory lability has been induced. Here, we attempted to replicate the classic finding that systemic administration of propranolol disrupts the reconsolidation of a pavlovian auditory fear memory. Following a failure to replicate, we manipulated the parameters of the memory reactivation session to enhance prediction error in an attempt to overcome the boundary conditions of reconsolidation. On finding no disruption of memory despite these manipulations, we examined the expression of the post-synaptic density protein Shank in the basolateral amygdala. Degradation of Shank has been shown to correlate with the induction of memory lability, but we found no effect on Shank expression, consistent with the lack of observed behavioural effects.

The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation.

Drug addiction can be seen as a disorder of maladaptive learning characterized by relapse. Therefore, disrupting drug-related memories could be an approach to improving therapies for addiction. Pioneering studies over the last two decades have revealed that consolidated memories are not static, but can be reconsolidated after retrieval, thereby providing candidate pathways for the treatment of addiction. The limbic–corticostriatal system is known to play a vital role in encoding the drug memory engram. Specific structures within this system contribute differently to the process of memory reconsolidation, making it a potential target for preventing relapse. In addition, as molecular processes are also active during memory reconsolidation, amnestic agents can be used to attenuate drug memory. In this review, we focus primarily on the brain structures involved in storing the drug memory engram, as well as the molecular processes involved in drug memory reconsolidation. Notably, we describe reports regarding boundary conditions constraining the therapeutic potential of memory reconsolidation. Furthermore, we discuss the principles that could be employed to modify stored memories. Finally, we emphasize the challenge of reconsolidation-based strategies, but end with an optimistic view on the development of reconsolidation theory for drug relapse prevention.

A Randomised Control Trial on the Effects of Fentanyl vs Subanaesthetic Dose of Ketamine given along with Propofol on Anaesthetic Profile and Recovery Characteristics

Introduction: Total Intravenous Anaesthesia (TIVA) has been a subject of interest for all anaesthesiologists. TIVA was initially attempted with a single drug but no drug was found to give complete anaesthesia. So, the technique of co-induction using two or more agents to induce anaesthesia has been studied. With the invention of newer induction agents, opioids and amnestic agents having shorter half-life, with advents of infusion pumps and depth of anaesthesia monitors like Bispectral Index (BIS), TIVA is gaining popularity day by day. Aim: To compare the effects of fentanyl or subanaesthetic dose of ketamine given along with propofol in TIVA. Materials and Methods: A randomised double blind study was conducted in patients who underwent elective laparotomy under TIVA. Sixty-two ASA grade I and II patients were randomised to receive either subanaesthetic dose of ketamine or fentanyl along with propofol for induction. Infusion of one of the study drugs was continued during maintenance along with propofol infusion which was titrated to maintain BIS of 40-60. Vecuronium was used to provide muscle relaxation and bolus doses of fentanyl were given whenever additional analgesia was needed. Intraoperative propofol, vecuronium and additional fentanyl requirement, time for tracheal extubation and time for first postoperative analgesic request were recorded. Continuous data was analysed with Student’s t-test and categorical data was analysed with Chi-square test. A p-value less than 0.05 were considered statistically significant. Results: Immediately after induction, haemodynamics were more stable in the ketamine group when compared to the fentanyl group. There was also a significant decrease in propofol requirement (6.501±0.24 Vs 6.672±0.26 mg/kg/hr) and a delay in the request for first postoperative analgesia in ketamine group (57.50±38.20 vs 40.50±22.68 minutes). Conclusion: Pre-incisional bolus of subanaesthetic ketamine followed by an infusion intraoperatively maintains haemodynamic stability, provides analgesia, decreases propofol requirement and delays request for first postoperative analgesia.

Apparent reconsolidation interference without generalized amnesia

Memories remain dynamic after consolidation, and when reactivated, they can be rendered vulnerable to various pharmacological agents that disrupt the later expression of memory (i.e., amnesia). Such drug-induced post-reactivation amnesia has traditionally been studied in AAA experimental designs, where a memory is initially created for a stimulus A (be it a singular cue or a context) and later reactivated and tested through exposure to the exact same stimulus. Using a contextual fear conditioning procedure in rats and midazolam as amnestic agent, we recently demonstrated that drug-induced amnesia can also be obtained when memories are reactivated through exposure to a generalization stimulus (GS, context B) and later tested for that same generalization stimulus (ABB design). However, this amnestic intervention leaves fear expression intact when at test animals are instead presented with the original training stimulus (ABA design) or a novel generalization stimulus (ABC design). The underlying mechanisms of post-reactivation memory malleability and of MDZ-induced amnesia for a generalization context remain largely unknown. Here, we evaluated whether, like typical CS-mediated (or AAA) post-reactivation amnesia, GS-mediated (ABB) post-reactivation amnesia displays key features of a destabilization-based phenomenon. We first show that ABB post-reactivation amnesia is critically dependent on prediction error at the time of memory reactivation and provide evidence for its temporally graded nature. In line with the known role of GluN2B-NMDA receptor activation in memory destabilization, we further demonstrate that pre-reactivation administration of ifenprodil, a selective antagonist of GluN2B-NMDA receptors, prevents MDZ-induced ABB amnesia. In sum, our data reveal that ABB MDZ-induced post-reactivation amnesia exhibits the hallmark features of a destabilization-dependent phenomenon. Implication of our findings for a reconsolidation-based account of post-reactivation amnesia are discussed.

Retrieval-Extinction and Relapse Prevention: Rewriting Maladaptive Drug Memories?

Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; “drug cues”) even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation—by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form—has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse. Furthermore, recent work has suggested that extinction training “within the reconsolidation window” may lead to a long-term reduction in relapse without the requirement for pharmacological amnestic agents. However, this so-called “retrieval-extinction” effect has been inconsistently observed in the literature, leading some to speculate that rather than reflecting memory updating, it may be the product of facilitation of extinction. In this mini review article, we will focus on factors that might be responsible for the retrieval-extinction effects on preventing drug-seeking relapse and how inter-individual differences may influence this therapeutically promising effect. A better understanding of the psychological and neurobiological mechanisms underpinning the “retrieval-extinction” paradigm, and individual differences in boundary conditions, should provide insights with the potential to optimize the translation of “retrieval-extinction” to clinical populations.

Regulation of Garcinol on Histone Acetylation in the Amygdala and on the Reconsolidation of a Cocaine-Associated Memory.

Exposure to drug-related cues often disrupts abstinence from cocaine use by triggering memories of drug effects, leading to craving and possible relapse. One prospective method of treatment is weakening cocaine-associated memories via impairment of memory reconsolidation. Previous experiments have shown that systemic injection of the amnestic agent garcinol impairs the reconsolidation of cocaine-cue memories in a temporally constrained, cue-specific, and persistent manner. Here, we investigated garcinol’s effect on cocaine-cue memory reconsolidation when administered to the lateral nucleus of the amygdala (LA), as well as its epigenetic activity following systemic garcinol administration and also when given in conjunction with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor. Rats received 12 days of cocaine self-administration training during which time an active lever press resulted in an i.v. cocaine infusion that was concurrently paired with the presentation of a light/tone cue. After 8 days of lever extinction, rats received a memory reactivation session followed by a cue-induced reinstatement test. Intra-LA garcinol following memory reactivation significantly impaired reconsolidation only if the memory was reactivated. Additional studies revealed a significant reduction in histone H3 K27 acetylation and reduced expression of the immediate-early genes Arc and Egr-1 in the LA. When administered alone, TSA enhanced the reinstatement of a cocaine-cue memory, an effect that was prevented when garcinol was concurrently administered. These data indicate the LA is a key structure responsive to garcinol, suggest that one of garcinol’s mechanisms of action is through the reduction of memory-related gene expression in the LA, implicate changes in histone acetylation in memory reconsolidation, and support garcinol as a potential therapeutic tool for sustaining abstinence.

Learning and memory enhancing properties of coenzyme Q10 in amnestic albino Wistar rats

Background: The brain is the important part of the nervous system in all vertebrates. The hippocampus in the humans serves as a major component of the brain. It is a part of the limbic system and plays major roles in acquiring long-term memory and spatial navigation. Among all dementia, Alzheimer’s dementia is most common. The affected person experiences inability to learn new information, has nominal and comprehensive aphasia, apraxia, agnosia, and impairment in execution of functioning. Coenzyme Q10 (Co-Q10) is a lipophilic molecule found, especially in high concentration in the mitochondrial inner membrane. The importance of Co-Q10 in mitochondrial function and its role as an antioxidant have led to therapeutic applications and clinical trials in degenerative diseases. Aim and Objective: This study aims to evaluate the learning and memory enhancing properties of Co-Q10 in albino Wistar rats. Materials and Methods: Eighteen healthy rats were selected for the study, which were divided into three groups. Scopolamine was used as amnestic agent, elevated plus maze (EPM), pole climbing test, and novel object recognition (NOR) tests were used for testing the learning and memory processes. Results: Co-Q10 at higher doses (400 mg/kg) showed significant activity in EPM, pole climbing test, and NOR test for assessing the learning and memory skills when compared to the control group. Conclusion: The present study results revealed that Co-Q10 high doses potentiated the process of learning and memory skills when tested using EPM, pole climbing test, and NOR test which are considered as standard paradigms of learning and memory screening models. The results of this study need to be further evaluated by comprehensive experimental studies and further validated by clinical trials.

The amnestic agent anisomycin disrupts intrinsic membrane properties of hippocampal neurons via a loss of cellular energetics.

The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary.NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.

Reconsolidation blockade for the treatment of addiction: challenges, new targets, and opportunities

Addiction is a chronic, relapsing disorder. The progression to pathological drug-seeking is thought to be driven by maladaptive learning processes which store and maintain associative memory, linking drug highs with cues and actions in the environment. These memories can encode Pavlovian associations which link predictive stimuli (e.g., people, places, and paraphernalia) with a hedonic drug high, as well as instrumental learning about the actions required to obtain drug-associated incentives. Learned memories are not permanent however, and much recent interest has been generated in exploiting the process of reconsolidation to erase or significantly weaken maladaptive memories to treat several mental health disorders, including addictions. Normally reconsolidation serves to update and maintain the adaptive relevance of memories, however administration of amnestic agents within the critical “reconsolidation window” can weaken or even erase maladaptive memories. Here we discuss recent advances in the field, including ongoing efforts to translate preclinical reconsolidation research in animal models into clinical practice.

The surprising subtleties of changing fear memory: a challenge for translational science.

Current pharmacological and psychological treatments for disorders of emotional memory only dampen the affective response while leaving the original fear memory intact. Under adverse circumstances, these original memories regain prominence, causing relapses in many patients. The (re)discovery in neuroscience that after reactivation consolidated fear memories may return to a transient labile state, requiring a process of restabilization in order to persist, offers a window of opportunity for modifying fear memories with amnestic agents. This process, known as memory reconsolidation, opens avenues for developing a revolutionary treatment for emotional memory disorders. The reconsolidation intervention challenges the dominant pharmacological and psychological models of treatment: it is only effective when the amnestic drug is given in conjunction with memory reactivation during a specific time window, and a modification of cognitive processes is a boundary condition for changing fear. Notwithstanding the dramatic effects of targeting memory reconsolidation in the laboratory (i.e. proof of principle), the greatest hurdle to overcome is that the success of the manipulation depends on subtle differences in the reactivation procedure. These experimental parameters cannot be easily controlled in clinical practice. In harnessing the clinical potential of memory reconsolidation, a heuristic for bi-directionally translating behavioural neuroscience and clinical science is proposed.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

Contextual fear conditioning in zebrafish.

Zebrafish are a genetically tractable vertebrate that hold considerable promise for elucidating the molecular basis of behavior. Although numerous recent advances have been made in the ability to precisely manipulate the zebrafish genome, much less is known about many aspects of learning and memory in adult fish. Here, we describe the development of a contextual fear conditioning paradigm using an electric shock as the aversive stimulus. We find that contextual fear conditioning is modulated by shock intensity, prevented by an established amnestic agent (MK-801), lasts at least 14 d, and exhibits extinction. Furthermore, fish of various background strains (AB, Tu, and TL) are able to acquire fear conditioning, but differ in fear extinction rates. Taken together, we find that contextual fear conditioning in zebrafish shares many similarities with the widely used contextual fear conditioning paradigm in rodents. Combined with the amenability of genetic manipulation in zebrafish, we anticipate that our paradigm will prove to be a useful complementary system in which to examine the molecular basis of vertebrate learning and memory.

Network oscillatory activity driven by context memory processing is differently regulated by glutamatergic and cholinergic neurotransmission

Memory retrieval requires coordinated intra- and inter-regional activity in networks of brain structures. Dysfunction of these networks and memory impairment are seen in many psychiatric disorders, but relatively little is known about how memory retrieval and memory failure are represented at the level of local and regional oscillatory activity. To address this question, we measured local field potentials (LFPs) from mice as they explored a novel context, retrieved memories for contextual fear conditioning, and after administration of two amnestic agents: the NMDA receptor antagonist MK-801 and muscarinic acetylcholine receptor antagonist scopolamine (SCOP). LFPs were simultaneously recorded from retrosplenial cortex (RSC), dorsal hippocampus (DH), and anterior cingulate cortex (ACC), which are involved in processing contextual memories, and analyzed for changes in intra-regional power and inter-regional peak coherence of oscillations across multiple frequency bands. Context encoding and memory retrieval sessions yielded similar patterns of changes across all three structures, including decreased delta power and increased theta peak coherence. Baseline effects of MK-801 and SCOP were primarily targeted to gamma oscillations, but in opposite directions. Both drugs also blocked memory retrieval, as indicated by reduced freezing when mice were returned to the conditioning context, but this common behavioral impairment was only associated with power and peak coherence disruptions after MK-801 treatment. These findings point to neural signatures for memory impairment, whose underlying mechanisms may serve as therapeutic targets for related psychiatric disorders.

Pharmacologic Considerations for Pediatric Sedation and Anesthesia Outside the Operating Room: A Review for Anesthesia and Non-Anesthesia Providers.

Understanding the pharmacologic options for pediatric sedation outside the operating room will allow practitioners to formulate an ideal anesthetic plan, allaying anxiety and achieving optimal immobilization while ensuring rapid and efficient recovery. The authors identified relevant medical literature by searching PubMed, MEDLINE, Embase, Scopus, Web of Science, and Google Scholar databases for English language publications covering a period from 1984 to 2017. Search terms included pediatric anesthesia, pediatric sedation, non-operating room sedation, sedation safety, and pharmacology. As a narrative review of common sedation/anesthesia options, the authors elected to focus on studies, reviews, and case reports that show clinical relevance to modern day sedation/anesthesia practice. A variety of pharmacologic agents are available for sedation/anesthesia in pediatrics, including midazolam, fentanyl, ketamine, dexmedetomidine, etomidate, and propofol. Dosing ranges reported are a combination of what is discussed in the reviewed literature and text books along with personal recommendations based on our own practice. Several reports reveal that ketofol (a combination of ketamine and propofol) is quite popular for short, painful procedures. Fospropofol is a newer-generation propofol that may confer advantages over regular propofol. Remimazolam combines the pharmacologic effects of remifentanil and midazolam. A variety of etomidate derivatives such as methoxycarbonyl-etomidate, carboetomidate, methoxycarbonyl-carboetomidate, and cyclopropyl-methoxycarbonyl metomidate are in development stages. The use of nitrous oxide as a mild sedative, analgesic, and amnestic agent is gaining popularity, especially in the ambulatory setting. Utilizing a dedicated and experienced team to provide sedation enhances safety. Furthermore, limiting sedation plans to single-agent pharmacy appears to be safer than using multi-agent plans.

Propofol sedation in children: sleep trumps amnesia

ObjectiveDetailed assessments of the effects of propofol on memory in children are lacking. We assessed the feasibility of measuring memory during propofol infusion, as commonly performed in sedation for MRI scanning. In addition, we determined the onset of memory loss in relation to the onset of sedation measured by verbal responsiveness. Materials and methodsChildren scheduled for sedation for MRI received a 10-min infusion of propofol (3 mg/kg) as they viewed and named 100 simple line drawings, one shown every five seconds, until they were no longer responsive (encoding). A control group receiving no sedation for MRI underwent similar tasks. Sedation was measured as any verbal response, regardless of correctness. After recovery from sedation, recognition memory was tested, with correct yes/no recognitions matched to sedation responses during encoding (subsequent memory paradigm). ResultsOf the 48 children who received propofol, 30 could complete all study tasks (6.2 ± 1.6 years, 16 males). Individual responses could be modeled in all 30 children. On average, there was a 50% probability of no verbal response 3.1 min after the start of infusion, with 50% memory loss at 2.7 min. Children receiving propofol recognized 65 ± 16% of the pictures seen, whereas the control group recognized 93 ± 5%. ConclusionMeasurement of memory and sedation is possible in verbal children receiving propofol by infusion in a clinical setting. Despite propofol being an amnestic agent, there was little or no amnestic effect of propofol while the child was verbally responsive. It is important for sedation providers to realize that propofol sedation does not always produce amnesia while the child is responsive. ClinicalTrials.gov numberNCT02278003.

The influence of washing methods on the DNA damage levels assessed by Comet assay

Detailed assessments of the effects of propofol on memory in children are lacking. We assessed the feasibility of measuring memory during propofol infusion, as commonly performed in sedation for MRI scanning. In addition, we determined the onset of memory loss in relation to the onset of sedation measured by verbal responsiveness.Children scheduled for sedation for MRI received a 10-min infusion of propofol (3 mg/kg) as they viewed and named 100 simple line drawings, one shown every five seconds, until they were no longer responsive (encoding). A control group receiving no sedation for MRI underwent similar tasks. Sedation was measured as any verbal response, regardless of correctness. After recovery from sedation, recognition memory was tested, with correct yes/no recognitions matched to sedation responses during encoding (subsequent memory paradigm).Of the 48 children who received propofol, 30 could complete all study tasks (6.2 ± 1.6 years, 16 males). Individual responses could be modeled in all 30 children. On average, there was a 50% probability of no verbal response 3.1 min after the start of infusion, with 50% memory loss at 2.7 min. Children receiving propofol recognized 65 ± 16% of the pictures seen, whereas the control group recognized 93 ± 5%.Measurement of memory and sedation is possible in verbal children receiving propofol by infusion in a clinical setting. Despite propofol being an amnestic agent, there was little or no amnestic effect of propofol while the child was verbally responsive. It is important for sedation providers to realize that propofol sedation does not always produce amnesia while the child is responsive.NCT02278003.