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Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
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Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo , Ansiedade , Humanos , Cápsula Interna , Transtorno Obsessivo-Compulsivo/terapia , Estudos Prospectivos , Resultado do TratamentoRESUMO
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.
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Amnésia/induzido quimicamente , Percepção Auditiva , Medo/psicologia , Memória/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
With the ultimate goal of investigating boundary conditions for post-reactivation amnesia, we set out to replicate studies in which systemic, post-reactivation administration of midazolam, propranolol, or cycloheximide resulted in amnesia for contextual fear memories. Our experiments involved conceptual as well as exact replications of previously published studies. In most of our experiments, we adopted a procedure that conformed to the standard 3-day protocol typically used in the literature, with contextual fear conditioning on day 1, unreinforced re-exposure to the conditioning context followed by systemic injection of the amnestic drug on day 2, and a memory retention test on day 3. Given the plethora of successful studies with large effects sizes and the absence of any failed replications in the literature, we were surprised to find that we were generally unable to replicate those findings. Our results suggest that post-reactivation amnesia by systemic drug administration in rats is more difficult to obtain than what would be expected based on published empirical reports. At present, it remains unclear which conditions determine the success of this procedure.
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Amnésia/induzido quimicamente , Medo/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Rememoração Mental/efeitos dos fármacos , Midazolam/administração & dosagem , Propranolol/administração & dosagem , Animais , Condicionamento Psicológico , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The amygdala and, more recently, also the bed nucleus of the stria terminalis, have been widely implicated in fear and anxiety. Much of our current knowledge is derived from animal studies and suggests an intricate convergence and divergence in functions related to defensive responding. In a recent paper, Klumpers and colleagues set out to examine these functions in a human fear learning procedure using functional magnetic resonance imaging. Their main findings were a role for the bed nucleus of the stria terminalis in threat anticipation, and for the amygdala in threat confrontation. Here, we provide a critical summary of this interesting study and point out some important issues that were not addressed by its authors. In particular, we first take a closer look at the striking differences between both samples that were combined for the study, and, secondly, we provide an in-depth discussion of their findings in relation to existing neurobehavioral models.
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Tonsila do Cerebelo/fisiologia , Antecipação Psicológica/fisiologia , Medo/fisiologia , Aprendizagem/fisiologia , Núcleos Septais/fisiologia , Animais , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Modelos NeurológicosRESUMO
BACKGROUND: From 1999 onwards, deep brain stimulation (DBS) has been proposed as an alternative to capsulotomy in refractory cases of obsessive-compulsive disorder (OCD). Although rechargeable implantable pulse generators (rIPGs) have been used extensively in DBS for movement disorders, there are no reports on rIPGs in patients with a psychiatric DBS indication, and even possible objections to their use. OBJECTIVE: We aim to evaluate rIPGs in OCD in terms of effectiveness, applicability, safety, and need for IPG replacement. METHODS: In this prospective before-after study recruiting from 2007 until 2012, OCD patients requiring at least one IPG replacement per 18 months were proposed to have a rIPG implanted at the next IPG depletion. OCD severity was the primary outcome. Ten patients were analyzed. RESULTS: Psychiatric symptoms and global functioning remained stable in the two years after as compared to the two years before rIPG implantation. Over the same period, the prescribed OCD medication doses did not increase and the DBS stimulation parameters were largely unaltered. Until the end of the follow-up (mean 4¾ years; maximum seven years), the DBS-related surgery frequency decreased and there were no rIPG replacements. During the first few weeks after implantation, two patients obsessively checked the rIPG, but afterwards there were no signs of compulsively checking or recharging the rIPG. Two patients experienced rIPG overdischarges (five occurrences in total). CONCLUSIONS: This is the first report on rIPGs in DBS for OCD patients. The use of rIPGs in this population appears to be effective, applicable, and safe and diminishes the need for IPG replacements.
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Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Fontes de Energia Elétrica , Eletrodos Implantados , Transtorno Obsessivo-Compulsivo/terapia , Adulto , Antidepressivos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
In 2009, Monfils and colleagues proposed a behavioral procedure that was said to result in a permanent attenuation of a previously established fear memory, thereby precluding a possible return of fear after extinction (Monfils, Cowansage, Klann, & LeDoux, 2009). By presenting a single retrieval trial one hour before standard extinction training, they found an enduring reduction of fear. The retrieval-extinction procedure holds great clinical potential, particularly for anxiety patients, but the findings are not undisputed, and several conceptual replications have failed to reproduce the effect. These failures have largely been attributed to small procedural differences. This preregistered study is the first endeavor to exactly replicate three key experiments of the original report by Monfils et al. (2009), thereby gauging the robustness of their seminal findings. Despite adhering to the original procedures as closely as possible, we did not find any evidence for reduced return of fear with the retrieval-extinction procedure relative to regular extinction training, as assessed through spontaneous recovery, reinstatement and renewal. Behavior of animals in the control condition (extinction only) was comparable to that in the original studies and provided an adequate baseline to reveal differences with the retrieval-extinction condition. Our null findings indicate that the effect sizes in the original paper may have been inflated and question the legitimacy of previously proposed moderators of the retrieval-extinction effect. We argue that direct experimental evaluation of purported moderators of the retrieval-extinction effect will be key to shed more light on its nature and prerequisites.
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Condicionamento Clássico , Extinção Psicológica , Medo , Rememoração Mental , Animais , Sinais (Psicologia) , Masculino , Ratos Sprague-DawleyRESUMO
Mather and colleagues postulate that norepinephrine promotes selective processing of emotionally salient information through local "hotspots" where norepinephrine release interacts with glutamatergic activity. However, findings in rodents and humans indicate that norepinephrine is ineffective in modulating mnemonic processes in the absence of a functional amygdala. We therefore argue that emphasis should shift toward modulatory effects of amygdala-driven changes at the network level.
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Tonsila do Cerebelo/fisiologia , Nível de Alerta , Emoções , Memória , Humanos , Norepinefrina/fisiologiaRESUMO
Instead of converging to one, all-embracing resilience mechanism - that is, positive appraisal style - we encourage complementary research strategies, exploring both vulnerabilities and resilience factors, much like the biomedical sciences combine insights from pathophysiology and immunology. Furthermore, we argue that research with a strong focus on one central resilience mechanism may overlook or undervalue other processes that can aid in maintaining mental health.
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Transtornos Mentais , Resiliência Psicológica , Humanos , Sistema Imunitário , Saúde MentalRESUMO
Pervasive avoidance is one of the central symptoms of all anxiety-related disorders. In treatment, avoidance behaviors are typically discouraged because they are assumed to maintain anxiety. Yet, it is not clear if engaging in avoidance is always detrimental. In this study, we used a platform-mediated avoidance task to investigate the influence of avoidance history on extinction learning in male rats. Our results show that having the opportunity to avoid during fear acquisition training does not significantly influence the extinction of auditory-cued fear in rats subjected to this platform-mediated avoidance procedure, which constitutes a realistic approach/avoidance conflict. This holds true irrespective of whether or not avoidance was possible during the extinction phase. This suggests that imposing a realistic cost on avoidance behavior prevents the adverse effects that avoidance has been claimed to have on extinction. However, avoidance does not appear to have clear positive effects on extinction learning nor on retention either.
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BACKGROUND: The neurotransmitter dopamine plays an important role in the processing of emotional memories, and prior research suggests that dopaminergic manipulations immediately after fear learning can affect the retention and generalization of acquired fear. AIMS: The current study focuses specifically on the role of dopamine D2 receptors (D2Rs) regarding fear generalization in adult, male Wistar rats, and aims to replicate previous findings in mice. METHODS: In a series of five experiments, D2R (ant)agonists were injected systemically, immediately after differential cued fear conditioning (CS+ followed by shock, CS- without shock). All five experiments involved the administration of the D2R agonist quinpirole at different doses versus saline (n = 12, 16, or 44 rats/group). In addition, one of the studies administered the D2R antagonist raclopride (n = 12). One day later, freezing during the CS+ and CS- was assessed. RESULTS: We found no indications for an effect of quinpirole or raclopride on fear generalization during this drug-free test. Importantly, and contradicting earlier research in mice, the evidence for the absence of an effect of D2R agonist quinpirole (1 mg/kg) on fear generalization was substantial according to Bayesian analyses and was observed in a highly powered experiment (N = 87). We did find acute behavioral effects in line with the literature, for both quinpirole and raclopride in a locomotor activity test. CONCLUSION: In contrast with prior studies in mice, we have obtained evidence against a preventative effect of post-training D2R agonist quinpirole administration on subsequent fear generalization in rats.
Assuntos
Condicionamento Clássico , Agonistas de Dopamina , Medo , Generalização Psicológica , Quimpirol , Racloprida , Ratos Wistar , Receptores de Dopamina D2 , Animais , Medo/efeitos dos fármacos , Masculino , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/metabolismo , Quimpirol/farmacologia , Agonistas de Dopamina/farmacologia , Ratos , Generalização Psicológica/efeitos dos fármacos , Racloprida/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Antagonistas dos Receptores de Dopamina D2/farmacologiaRESUMO
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Assuntos
Antagonistas Adrenérgicos beta , Extinção Psicológica , Medo , Memória , Midazolam , Propranolol , Propranolol/farmacologia , Propranolol/administração & dosagem , Animais , Medo/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Ratos , Humanos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/administração & dosagem , Masculino , Memória/efeitos dos fármacos , Midazolam/farmacologia , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Adulto , Teorema de Bayes , Feminino , Condicionamento Clássico/efeitos dos fármacos , Adulto JovemRESUMO
Using (18)F-fluorodeoxyglucose microPET imaging, we investigated the neurocircuitry of contextual anxiety versus control in awake, conditioned rats (n = 7-10 per group). In addition, we imaged a group expressing cued fear. Simultaneous measurements of startle amplitude and freezing time were used to assess conditioning. To the best of our knowledge, no neuroimaging studies in conditioned rats have been conducted thus far, although visualizing and quantifying the metabolism of the intact brain in behaving animals is clearly of interest. In addition, more insight into the neurocircuitry involved in contextual anxiety may stimulate the development of new treatments for anxiety disorders. Our main finding was hypermetabolism in a cluster comprising the bed nucleus of the stria terminalis (BST) in rats expressing contextual anxiety compared with controls. Analysis of a subset of rats showing the best behavioral results (n = 5 per subgroup) confirmed this finding. We also observed hypermetabolism in the same cluster in rats expressing contextual anxiety compared with rats expressing cued fear. Our results provide novel evidence for a role of the BST in the expression of contextual anxiety.
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Ansiedade/metabolismo , Condicionamento Psicológico/fisiologia , Metabolismo Energético/fisiologia , Tomografia por Emissão de Pósitrons/métodos , Núcleos Septais/diagnóstico por imagem , Núcleos Septais/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Vias Neurais/fisiologia , Ratos , Ratos Wistar , Núcleos Septais/anatomia & histologiaRESUMO
Re-exposure to elements of prior experiences can create opportunities for inducing amnesia for those events. The dominant theoretical framework posits that such re-exposure can result in memory destabilization, making the memory representation temporarily sensitive to disruption while it awaits reconsolidation. If true, such a mechanism that allows for memories to be permanently changed could have important implications for the treatment of several forms of psychopathology. However, there have been contradictory findings and elusive occurrences of replication failures within the "reconsolidation" field. Considering its potential relevance for clinical applications, the fact that this "hot" research area is being dominated by a single mechanistic theory, and the presence of unexplainable contradictory findings, we believe that it is both useful and timely to critically evaluate the reconsolidation framework. We discuss potential issues that may arise from how reconsolidation interference has typically been deducted from behavioral observations, and provide a principled assessment of reconsolidation theory that illustrates that the theory and its proposed boundary conditions are vaguely defined, which has made it close to impossible to refute reconsolidation theory. We advocate for caution, encouraging researchers not to blindly assume that a reconsolidation process must underlie their findings, and pointing out the risks of doing so. Finally, we suggest concrete theoretical and methodological advances that can promote a fruitful translation of reminder-dependent amnesia into clinical treatment.
Assuntos
Consolidação da Memória , Memória , Humanos , AmnésiaRESUMO
Fear is an adaptive emotion that mobilizes defensive resources upon confrontation with danger. However, fear becomes maladaptive and can give rise to the development of clinical anxiety when it exceeds the degree of threat, generalizes broadly across stimuli and contexts, persists after the danger is gone or promotes excessive avoidance behaviour. Pavlovian fear conditioning has been the prime research instrument that has led to substantial progress in understanding the multi-faceted psychological and neurobiological mechanisms of fear in past decades. In this Perspective, we suggest that fruitful use of Pavlovian fear conditioning as a laboratory model of clinical anxiety requires moving beyond the study of fear acquisition to associated fear conditioning phenomena: fear extinction, generalization of conditioned fear and fearful avoidance. Understanding individual differences in each of these phenomena, not only in isolation but also in how they interact, will further strengthen the external validity of the fear conditioning model as a tool with which to study maladaptive fear as it manifests in clinical anxiety.
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In the face of a possible threat, a range of physiological (e.g., increased heart rate) and behavioral (e.g., avoidance or escape) responses are recruited. Here, we will focus on avoidance, in its persistent form one of the core symptoms of anxiety disorders and obsessive-compulsive disorder. The initial goal of fear and avoidance responses is to increase survival, but if they become persistent or overgeneralize, they can disrupt normal daily functioning, and ultimately even result in anxiety-related disorders. Relatedly, acute stress responses promote adaptation and survival, while chronic stress has been found to aggravate pathophysiology. Thus, stress might trigger the transition from adaptive to maladaptive responses, e.g., from goal-directed to persistent avoidance. Animal models are prime tools to unravel if and how stress influences avoidance. This is typically done by performing stress inductions prior to the assessment of (passive or active) avoidance behavior. Despite its clinical relevance, the current literature on this topic is fragmented, and an overall conclusion is lacking. In this Review, we first recapitulate the state of the art regarding stress and active as well as passive avoidance procedures. We then summarize the behavioral effects of acute and chronic stress on active and passive avoidance, and discuss the main neurobiological findings of the field. Finally, we highlight possible reasons for the largely contradictory findings in the literature and we propose strategies to further unravel the effect of stress on avoidance behavior. A deeper understanding of this currently unresolved matter may provide further insights in the etiology and treatment of anxiety-related disorders.
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BACKGROUND: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant obsessive-compulsive disorder (OCD), and several targets for electrode implantation and contact selection have been proposed, including the bed nucleus of the stria terminalis (BST). Selecting the active electrode contacts (patients typically have four to choose from in each hemisphere), and thus the main locus of stimulation, can be a taxing process. Here, we investigated whether contact selection based purely on their neuroanatomical position in the BST is a worthwhile approach. For the first time, we also compared the effects of uni- versus bilateral BST stimulation. METHODS: Nine OCD patients currently receiving DBS participated in a double-blind, randomized symptom provocation study to compare no versus BST stimulation. Primary outcomes were anxiety and mood ratings in response to disorder-relevant trigger images, as well as ratings of obsessions, compulsions, tendency to avoid and overall wellbeing. Furthermore, we asked whether patients preferred the electrode contacts in the BST over their regular stimulation contacts as a new treatment setting after the end of the task. RESULTS: We found no statistically significant group differences between the four conditions (no, left, right and bilateral BST stimulation). Exploratory analyses, as well as follow-up data, did indicate that (bilateral) bipolar stimulation in the BST was beneficial for some patients, particularly for those who had achieved unsatisfactory effects through the typical contact selection procedure. CONCLUSIONS: Despite its limitations, this study suggests that selection of stimulation contacts in the BST is a viable option for DBS in treatment-resistant OCD patients.
Assuntos
Estimulação Encefálica Profunda , Transtorno Obsessivo-Compulsivo , Núcleos Septais , Ansiedade , Estimulação Encefálica Profunda/métodos , Método Duplo-Cego , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Núcleos Septais/fisiologia , Tálamo , Resultado do TratamentoRESUMO
Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD.
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Transtornos de Ansiedade/psicologia , Condicionamento Psicológico , Modelos Animais de Doenças , Animais , Ansiedade , Medo , Humanos , Ratos , Estudos de Validação como AssuntoRESUMO
Research on memory reconsolidation has been booming in the last two decades, with numerous high-impact publications reporting promising amnestic interventions in rodents and humans. However, our own recently-published failed replication attempts of reactivation-dependent amnesia for fear memories in rats suggest that such amnestic effects are not always readily found and that they depend on subtle and possibly uncontrollable parameters. The discrepancy between our observations and published studies in rodents suggests that the literature in this field might be biased. The aim of the current study was to gauge the presence of publication bias in a well-delineated part of the reconsolidation literature. To this end, we performed a systematic review of the literature on reactivation-dependent amnesia for contextual fear memories in rodents, followed by a statistical assessment of publication bias in this sample. In addition, relevant researchers were contacted for unpublished results, which were included in the current analyses. The obtained results support the presence of publication bias, suggesting that the literature provides an overly optimistic overall estimate of the size and reproducibility of amnestic effects. Reactivation-dependent amnesia for contextual fear memories in rodents is thus less robust than what is projected by the literature. The moderate success of clinical studies may be in line with this conclusion, rather than reflecting translational issues. For the field to evolve, replication and non-biased publication of obtained results are essential. A set of tools that can create opportunities to increase transparency, reproducibility and credibility of research findings is provided.
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Medo , Memória , Amnésia , Animais , Viés de Publicação , Ratos , Reprodutibilidade dos TestesRESUMO
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.
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Rememoração Mental/efeitos dos fármacos , Midazolam/farmacologia , Retenção Psicológica/efeitos dos fármacos , Animais , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Medo/psicologia , Generalização Psicológica/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
Recent clinical evidence has put forward a new region of interest for the treatment of psychiatric disorders. Deep brain stimulation in the bed nucleus of the stria terminalis (BST) significantly attenuates symptoms in patients suffering from severe, treatment-resistant obsessive-compulsive disorder (OCD). The BST is not typically implicated in OCD neuropsychopathology but is certainly not an unknown in the field of emotional learning and memory. Substantial evidence supports its involvement in anxiety responses, particularly to ambiguous threats. This seems consistent with the intolerance of uncertainty and tendency to overestimate danger, which fuel obsessions and compulsions in many patients with OCD. Translational research in rodents can help to obtain a deeper understanding of the effects of high-frequency electrical stimulation in the BST on anxiety, which may be valuable to improve treatment for psychiatric patients.