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Biased choice and incentive salience: Implications for addiction. 偏差选择和激励突出:对成瘾的影响。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1037/bne0000583
Mike E Le Pelley, Poppy Watson, Reinout W Wiers

Before we can make any choice, we must gather information from the environment about what our options are. This information-gathering process is critically mediated by attention, and our attention is, in turn, shaped by our previous experiences with-and learning about-stimuli and their consequences. In this review, we highlight studies demonstrating a rapid and automatic influence of reward learning on attentional capture and argue that these findings provide a human analog of sign-tracking behavior observed in nonhuman animals-wherein signals of reward gain incentive salience and become attractive targets for attention (and overt behavior) in their own right. We then consider the implications of this idea for understanding the drivers of cue-controlled behavior, with focus on addiction as a case in which choices with regard to reward-related stimuli can become injurious to health. We argue that motivated behavior in general-and addiction in particular-can be understood within a "biased competition" framework: Different options and outcomes compete for attentional priority as a function of top-down goals, bottom-up salience, and prior experience, and the winner of this competition becomes the target for subsequent outcome-directed and flexible behavior. Finally, we outline the implications of the biased-competition framework for cognitive, behavioral, and socioeconomic interventions for addiction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

在做出任何选择之前,我们必须从环境中收集信息,了解我们有哪些选择。这一信息收集过程主要以注意力为中介,而我们的注意力反过来又受我们以前对刺激及其后果的经验和学习的影响。在这篇综述中,我们将重点介绍证明奖励学习对注意力捕捉具有快速和自动影响的研究,并认为这些研究结果提供了在非人类动物身上观察到的标志追踪行为的人类类比--在这种行为中,奖励信号会获得激励显著性,并以其自身的方式成为吸引注意力(和公开行为)的目标。然后,我们将探讨这一观点对理解线索控制行为驱动因素的影响,并重点关注成瘾这一案例,因为在这种情况下,与奖赏相关的刺激选择可能会损害健康。我们认为,可以在 "偏向竞争 "框架内理解一般动机行为,尤其是成瘾行为:在自上而下的目标、自下而上的显著性和先前经验的作用下,不同的选择和结果会争夺注意力的优先权。最后,我们概述了偏向竞争框架对认知、行为和社会经济干预成瘾的影响。(PsycInfo Database Record (c) 2024 APA, all rights reserved)。
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引用次数: 0
Translational approaches to the neurobiological study of conditional discrimination and inhibition: Implications for psychiatric disease. 条件辨别和抑制神经生物学研究的转化方法:对精神疾病的影响。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-24 DOI: 10.1037/bne0000594
Susan Sangha, Jacklynn M Fitzgerald

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral and neural findings are reviewed among human and rodent studies that include conditional fear discrimination via conditional stimuli with and without reinforcement (CS+ vs. CS-, respectively) and/or conditional inhibition of fear through assessment of the fear response to a compound CS-/CS+ cue versus CS+. There are several parallels across species in behavioral fear expression as well as neural circuits promoting fear reduction in response to a CS- and/or CS-/CS+ compound cue. Continued and increased efforts to compare similar behavioral fear inhibition paradigms across species are needed to make breakthrough advances in our understanding and treatment approaches to individuals with fear disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

越来越多的研究调查了辨别性恐惧条件反射和条件性恐惧抑制,以评估安全学习,以及提示性恐惧的消退。尽管所有这些范式都会导致恐惧表达的减少,但它们之间存在着细微的差异,这些差异可能是通过不同的行为和神经机制介导的。这些差异可能会影响我们如何在临床上治疗恐惧反应失调的疾病。本综述旨在概述在动物模型和人类神经精神疾病中报道的条件辨别和抑制结果。本文综述了人类和啮齿类动物的行为和神经研究结果,这些研究包括通过有强化和无强化的条件刺激(分别为 CS+ 和 CS-)进行的条件性恐惧辨别,以及/或通过评估对 CS-/CS+ 和 CS+ 复合线索的恐惧反应进行的条件性恐惧抑制。不同物种在行为恐惧表达以及神经回路方面存在若干相似之处,这些神经回路可促进对 CS- 和/或 CS-/CS+ 复合线索的恐惧反应的减少。我们需要继续加大力度比较不同物种间类似的行为恐惧抑制范式,以便在理解和治疗恐惧障碍患者方面取得突破性进展。(PsycInfo Database Record (c) 2024 APA,保留所有权利)。
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引用次数: 0
Resource-rational psychopathology. 资源理性精神病理学。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-16 DOI: 10.1037/bne0000600
Bilal A Bari, Samuel J Gershman

Psychopathology is vast and diverse. Across distinct disease states, individuals exhibit symptoms that appear counter to the standard view of rationality (expected utility maximization). We argue that some aspects of psychopathology can be described as resource-rational, reflecting a rational trade-off between reward and cognitive resources. We review work on two theories of this kind: rational inattention, where a capacity limit applies to perceptual channels, and policy compression, where the capacity limit applies to action channels. We show how these theories can parsimoniously explain many forms of psychopathology, including affective, primary psychotic, and neurodevelopmental disorders, as well as many effects of psychoactive medications on these disorders. While there are important disorder-specific differences and the theories are by no means universal, we argue that resource rationality offers a useful new perspective on psychopathology. By emphasizing the role of cognitive resource constraints, this approach offers a more inclusive picture of rationality. Some aspects of psychopathology may reflect rational trade-offs rather than the breakdown of rationality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

精神病理学种类繁多。在各种不同的疾病状态中,个体表现出的症状似乎与标准的理性观点(预期效用最大化)背道而驰。我们认为,精神病理学的某些方面可以被描述为资源理性,反映了报酬与认知资源之间的理性权衡。我们回顾了两种此类理论的研究成果:理性注意力不集中理论和政策压缩理论,前者认为感知通道受到能力限制,而后者则认为行动通道受到能力限制。我们展示了这些理论如何能够合理地解释多种形式的精神病理学,包括情感障碍、原发性精神病和神经发育障碍,以及精神活性药物对这些障碍的许多影响。虽然这些理论与特定疾病存在重大差异,也绝非放之四海而皆准,但我们认为,资源合理性为精神病理学提供了一个有用的新视角。通过强调认知资源限制的作用,这种方法为理性提供了一个更具包容性的图景。精神病理学的某些方面可能反映了理性的权衡,而不是理性的崩溃。(PsycInfo Database Record (c) 2024 APA, all rights reserved)。
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引用次数: 0
A psychological mechanism for the development of anxiety. 焦虑发展的心理机制
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 DOI: 10.1037/bne0000607
Gonzalo P Urcelay
Although numerous behavioral constructs have been proposed to account for anxiety disorders, how these disorders develop within an individual has been difficult to predict. In this perspective, I selectively review clinical and experimental evidence suggesting that avoidance (i.e., safety) behavior increases beliefs of threat or fear. The experimental evidence has been replicated numerous times, with different parameters, and shows that when human participants emit avoidance responses in the presence of a neutral stimulus, they later show heightened expectations of threat in the presence of the neutral stimulus. I interpret these findings as resulting from prediction errors as anticipated by the Rescorla-Wagner model, although other animal learning theories can also predict the phenomenon. I discuss some implications and offer a few novel predictions. The analysis presented here sheds light on a phenomenon of theoretical and clinical relevance which is accommodated by basic associative learning theory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
尽管已经提出了许多行为建构来解释焦虑症,但这些焦虑症是如何在个体内部发展的却很难预测。在这一观点中,我有选择性地回顾了临床和实验证据,这些证据表明回避(即安全)行为会增加对威胁或恐惧的信念。这些实验证据已经用不同的参数重复了无数次,结果表明,当人类参与者在中性刺激面前做出回避反应时,他们随后会在中性刺激面前表现出更高的威胁预期。尽管其他动物学习理论也能预测这一现象,但我将这些发现解释为雷斯克拉-瓦格纳模型所预期的预测错误所致。我讨论了一些影响,并提出了一些新的预测。本文的分析揭示了一种具有理论和临床意义的现象,这种现象可以被基本的联想学习理论所包容。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
Fear attenuation collaborations to optimize translation. 减弱恐惧合作,优化翻译。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-06-01 DOI: 10.1037/bne0000581
Marie-H Monfils, Hongjoo J Lee, Marissa Raskin, Yael Niv, Jason Shumake, Michael J Telch, Jasper A J Smits, Michael W Otto

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

在此,我们将介绍我们为改变根深蒂固的情感记忆所做的努力。近年来,我们通过多项合作,并结合使用行为、分子和计算方法:(a)开发了新的恐惧衰减方法,这些方法采用的机制与消退过程中采用的机制不同(蒙菲尔斯);(b)研究了我们的方法是否可以推广到其他强化物(李、冈萨雷斯、乔德里、科夫雷西和蒙菲尔斯);(c)得出了我们的方法产生不同结果的原理性解释(尼夫、格什曼、宋和蒙菲尔斯);(d)研究了我们的方法是否可以推广到其他强化物(李、冈萨雷斯、乔德里、科夫雷西和蒙菲尔斯)、Song和Monfils),(d)开发出更好的评估指标来评价结果的成功与否(Shumake和Monfils),(e)确定了能够解释我们所关注的结果的显著差异的生物标志物(Shumake和Monfils),以及(f)开发出更好的基础研究测定方法并将其应用于临床(Smits、Telch、Otto、Shumake和Monfils)。我们将简要介绍其中的每一个里程碑,并以最后的评论和提炼出的原则作为结束语。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
Prediction, perception, and psychosis: Application of associative learning theories to schizophrenia research. 预测、感知和精神病:联想学习理论在精神分裂症研究中的应用。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-06-01 DOI: 10.1037/bne0000599
Riria Suzuki, Yutaka Kosaki

In recent years, there have been significant advances in our understanding of the positive symptoms of schizophrenia, such as hallucinations and delusions. This progress has been significantly aided by the use of associative learning-based approaches in human subjects and preclinical animal models. Here, we first review experimental research focusing on the abnormal processing of absent stimuli using three different conditioning phenomena: conditioned hallucinations, mediated conditioning, and trace conditioning. We then review studies investigating the ability to reduce focal processing of physically present but informationally redundant stimuli using habituation, latent inhibition, and blocking. The results of these different lines of research are then summarized within the framework of Wagner's (1981) standard operating procedures model, an associative learning model with explicit reference to the internal representations of both present and absent stimuli. Within this framework, the central deficit associated with positive symptoms can be described as a failure to suppress the focal processing of both absent stimuli and present but irrelevant stimuli. This can explain the wide range of results obtained in different experimental settings. Finally, we briefly discuss the role of the hippocampus and its interaction with dopaminergic transmission in the emergence of such abnormal stimulus representations and learning. Overall, we hope that the theoretical framework and empirical findings offered by the associative learning approach will continue to facilitate and integrate analyses of schizophrenia conducted at the psychological and behavioral levels on the one hand, and at the neural and molecular levels on the other, by serving as a useful interface between them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

近年来,我们对幻觉和妄想等精神分裂症阳性症状的认识取得了重大进展。在人类受试者和临床前动物模型中使用基于联想学习的方法极大地促进了这一进展。在此,我们首先回顾了利用三种不同的条件反射现象(条件性幻觉、中介条件反射和追踪条件反射)对不存在的刺激进行异常处理的实验研究。然后,我们回顾了利用习惯化、潜在抑制和阻断来减少对物理上存在但信息上冗余的刺激的焦点处理能力的研究。然后,我们在瓦格纳(1981 年)的标准操作程序模型框架内总结了这些不同研究的结果,该模型是一个联想学习模型,明确参考了存在和不存在刺激的内部表征。在这一框架内,与阳性症状相关的中枢缺陷可被描述为未能抑制对不存在的刺激和存在但不相关的刺激的集中处理。这就可以解释在不同的实验环境下得到的各种结果。最后,我们简要讨论了海马体及其与多巴胺能传导的相互作用在出现这种异常刺激表征和学习中的作用。总之,我们希望联想学习方法所提供的理论框架和实证研究结果将继续促进和整合在心理和行为层面以及神经和分子层面对精神分裂症的分析,成为两者之间有用的接口。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
The role of midbrain dopamine cells projecting to the insular cortex in mediated performance: Implications for animal models of reality testing. 投射到岛叶皮层的中脑多巴胺细胞在中介表现中的作用:对现实测试动物模型的启示
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-06-01 DOI: 10.1037/bne0000580
Benjamin R Fry, Victoria Fex, Akira Sawa, Minae Niwa, Alexander W Johnson

A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric illness. In particular, recent work has shown that animal models that recapitulate various endophenotypes of schizophrenia are particularly vulnerable to impairments in reality testing when undergoing mediated learning. Multiple studies have indicated that these effects are dopamine receptor 2-dependent and correlated with aberrant insular cortex (IC) activity. However, until now, the connection between dopamine and the IC had not been investigated. Here, we utilized a novel intersectional approach to label mesencephalic dopamine cells that specifically project to the insular cortex in both wild-type controls and transgenic mice expressing the dominant-negative form of the Disrupted-in-Schizophrenia-1 (DISC-1) gene. Using these techniques, we identified a population of cells that project from the ventral tegmental area (VTA) to the IC. Afterward, we conducted multiple studies to test the necessity of this circuit in behaviors ranging from gustatory detection to the maintenance of effort and, finally, mediated performance. Our results indicate that perturbations of the DISC-1 genetic locus lead to a reduction in the number of cells in the VTA → IC circuit. Behaviorally, VTA → IC circuitry does not influence gustatory detection or motivation to acquire sucrose reward; however, inactivation of this circuit differentially suppresses Pavlovian approach behavior in wild-type and DISC-1 transgenic mice during mediated performance testing. Moreover, under these testing conditions, inactivation of this circuit predisposes wild-type (but not DISC-1) mice to display impaired reality testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

越来越多的文献表明,中介学习技术在神经精神疾病动物模型的现实测试中具有特殊作用。特别是,最近的研究表明,再现精神分裂症各种内表型的动物模型在进行介导学习时特别容易受到现实测试障碍的影响。多项研究表明,这些影响依赖于多巴胺受体 2,并与异常的岛叶皮层(IC)活动相关。然而,到目前为止,多巴胺与岛叶皮层之间的联系尚未得到研究。在这里,我们采用了一种新颖的交叉方法来标记间脑多巴胺细胞,这些细胞特异性地投射到野生型对照组和表达显性阴性的精神分裂症干扰-1(DISC-1)基因的转基因小鼠的岛叶皮层。利用这些技术,我们确定了从腹侧被盖区(VTA)投射到 IC 的细胞群。随后,我们进行了多项研究,以检验这一回路在从味觉检测到维持努力等行为中的必要性,并最终检验了中介表现。我们的研究结果表明,DISC-1基因位点的干扰会导致VTA→IC回路中细胞数量的减少。在行为上,VTA → IC回路并不影响味觉检测或获取蔗糖奖励的动机;然而,在介导的表现测试中,野生型小鼠和DISC-1转基因小鼠的巴甫洛夫接近行为会受到不同程度的抑制。此外,在这些测试条件下,该回路的失活使野生型(而非 DISC-1)小鼠在现实测试中表现出受损的倾向。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
Brain electrical patterns associated with pleasure and emotion induced by tonal and atonal music. 调性音乐和无调性音乐诱发的与愉悦和情感相关的脑电模式。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-05-02 DOI: 10.1037/bne0000588
Pablo Valdés-Alemán, Bernarda Téllez-Alanís, Adriana Zamudio-Gurrola
Several studies in the last 40 years have used electroencephalography (EEG) to recognize patterns of brain electrical activity correlated with emotions evoked by various stimuli. For example, the frontal alpha and theta asymmetry models to distinguish musical emotions and musical pleasure, respectively. Since these studies have used mainly tonal music, in this study, we decided to incorporate both tonal (n = 8) and atonal (n = 8) musical stimuli to observe the subjective and electrophysiological responses associated with valence, arousal, pleasure, and familiarity, from 25 nonmusician Mexican adults (10 females, 15 males; M = 37.8 years old, SD = 15.1). Our results showed that atonal music was perceived as less familiar and pleasurable than tonal music, according to the average subjective ratings. Interestingly, greater right hemispheric activity (alpha suppression) was associated with atonal music listening. Additionally, there was an increase of theta power at the right frontal cortex (F4) correlated with a decrease of pleasure ratings, in line with the frontal theta asymmetry (FTA) model. Finally, according to the model of frontal alpha asymmetry (FAA) to distinguish musical emotions, activation (alpha suppression) of the left frontal cortex (F3) was correlated with greater valence and arousal-that is, joyful music. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
在过去的 40 年中,有多项研究利用脑电图(EEG)来识别与各种刺激引起的情绪相关的脑电活动模式。例如,额叶α和θ不对称模型分别用于区分音乐情绪和音乐愉悦。由于这些研究主要使用的是调性音乐,因此在本研究中,我们决定同时使用调性(n = 8)和无调性(n = 8)音乐刺激,以观察 25 名非音乐家的墨西哥成年人(10 名女性,15 名男性;男 = 37.8 岁,女 = 15.1 岁)与情绪、唤醒、愉悦和熟悉程度相关的主观反应和电生理反应。我们的研究结果表明,根据主观评分的平均值,人们对无调性音乐的熟悉度和愉悦感均低于对调性音乐的熟悉度和愉悦感。有趣的是,右半球活动(α抑制)与听无调性音乐有关。此外,右侧额叶皮层(F4)θ功率的增加与愉悦感评分的降低相关,这与额叶θ不对称(FTA)模型一致。最后,根据额叶α不对称(FAA)模型来区分音乐情绪,左侧额叶皮层(F3)的激活(α抑制)与更高的情绪和唤醒相关,即快乐的音乐。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years. 少即是多:海马亚区体积越小,预示着创伤后应激障碍症状在两年内的改善程度越大。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-04-25 DOI: 10.1037/bne0000578
Joseph DeGutis, Danielle R Sullivan, Sam Agnoli, Anna Stumps, Mark Logue, Emma Brown, Mieke Verfaellie, William Milberg, Regina McGlinchey, Michael Esterman
Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years. We examined clinical and structural magnetic resonance imaging measures from 252 trauma-exposed post-9/11 veterans (159 with Time 1 PTSD diagnosis) during assessments approximately 2 years apart. Automated hippocampal subfield segmentation was performed with FreeSurfer Version 7.1, producing 19 bilateral subfields. PTSD symptoms were measured at each assessment using the Clinician-Administered PTSD Scale-IV (CAPS). All models included total intracranial volume as a covariate. First, similar to previous reports, we showed that smaller overall hippocampal volume was associated with greater PTSD symptom severity at Time 1. Notably, when examining regions of interest (CA1, CA3, dentate gyrus), we found that smaller Time 1 hippocampal volumes in the bilateral CA1-body and CA2/3-body predicted decreased PTSD symptom severity at Time 2. These findings were not accounted for by combat exposure or treatment history. Additionally, both Time 1 CA1-body and CA2/3-body volume showed unique associations with changes in avoidance/numbing, but not with changes in reexperiencing or hyperarousal symptoms. This supports a more complex and nuanced relationship between hippocampal structure and PTSD symptoms, where during the posttrauma years bigger may not always mean better, and suggests that the CA1-body and CA2/3-body are important factors in the maintenance of PTSD symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
创伤后应激障碍(PTSD)是一种异质性疾病,症状的严重程度随时间而变化。预测创伤后应激障碍症状及其慢性化的神经生物学因素仍不清楚。本研究调查了海马及其亚区(尤其是粟粒1(CA)、CA3和齿状回)的体积是否与当前的创伤后应激障碍症状相关,以及它们是否能预测两年内创伤后应激障碍症状的变化。我们对 252 名 9/11 事件后受到创伤的退伍军人(其中 159 人被诊断为第一时间创伤后应激障碍)进行了临床和结构性磁共振成像测量,评估时间相隔约 2 年。使用 FreeSurfer 7.1 版对海马亚区进行了自动分割,产生了 19 个双侧亚区。每次评估都使用临床医师管理创伤后应激障碍量表-IV(CAPS)测量创伤后应激障碍症状。所有模型都将颅内总容积作为协变量。首先,与之前的报告类似,我们发现海马体总体积较小与时间 1 时创伤后应激障碍症状严重程度较高有关。值得注意的是,在研究相关区域(CA1、CA3、齿状回)时,我们发现时间1时双侧CA1-体和CA2/3-体的海马体积较小,这预示着时间2时创伤后应激障碍症状的严重程度会降低。这些研究结果并不能被战斗经历或治疗史所解释。此外,时间 1 CA1 体和 CA2/3 体的体积与回避/麻木症状的变化有独特的关联,但与再体验或过度焦虑症状的变化无关。这支持了海马结构与创伤后应激障碍症状之间更复杂、更微妙的关系,在创伤后的几年中,体积越大并不一定意味着越好,这表明CA1体和CA2/3体是维持创伤后应激障碍症状的重要因素。(PsycInfo Database Record (c) 2024 APA, 版权所有)。
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引用次数: 0
Indirect and direct cannabinoid agonists differentially affect mesolimbic dopamine release and related behaviors. 间接和直接大麻素激动剂对间叶多巴胺释放和相关行为的影响各不相同。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-04-25 DOI: 10.1037/bne0000582
Kevin M Honeywell, Timothy G Freels, Megan A McWain, Abigail S Chaffin, Hunter G Nolen, Helen J Sable, Deranda B Lester
The cannabinoid system is being researched as a potential pharmaceutical target for a multitude of disorders. The present study examined the effect of indirect and direct cannabinoid agonists on mesolimbic dopamine release and related behaviors in C57BL/6J (B6) mice. The indirect cannabinoid agonist N-arachidonoyl serotonin (AA-5-HT) indirectly agonizes the cannabinoid system by preventing the metabolism of endocannabinoids through fatty acid amide hydrolase inhibition while also inhibiting transient receptor potential vanilloid Type 1 channels. Effects of AA-5-HT were compared with the direct cannabinoid receptor Type 1 agonist arachidonoyl-2'-chloroethylamide (ACEA). In Experiment 1, mice were pretreated with seven daily injections of AA-5-HT, ACEA, or vehicle prior to assessments of locomotor activity using open field (OF) testing and phasic dopamine release using in vivo fixed potential amperometry. Chronic exposure to AA-5-HT did not alter locomotor activity or mesolimbic dopamine functioning. Chronic exposure to ACEA decreased rearing and decreased phasic dopamine release while increasing the dopaminergic response to cocaine. In Experiment 2, mice underwent AA-5-HT, ACEA, or vehicle conditioned place preference, then saccharin preference testing, a measure commonly associated with anhedonia. Mice did not develop a conditioned place preference or aversion for AA-5-HT or ACEA, and repeated exposure to AA-5-HT or ACEA did not alter saccharin preference. Altogether, the findings suggest that neither of these drugs induce behaviors that are classically associated with abuse liability in mice; however, direct cannabinoid receptor Type 1 agonism may play more of a role in mediating mesolimbic dopamine functioning than indirect cannabinoid agonism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
大麻素系统正被作为治疗多种疾病的潜在药物靶点进行研究。本研究考察了间接和直接大麻素激动剂对 C57BL/6J (B6) 小鼠间叶多巴胺释放和相关行为的影响。间接大麻素激动剂 N-arachidonoyl 血清素(AA-5-HT)通过抑制脂肪酸酰胺水解酶阻止内源性大麻素的代谢,同时抑制瞬时受体电位香草素 1 型通道,从而间接激动大麻素系统。我们将 AA-5-HT 的作用与直接大麻素受体 1 型激动剂花生四烯丙基-2'-氯乙基酰胺(ACEA)进行了比较。在实验 1 中,每天给小鼠注射七次 AA-5-HT、ACEA 或车辆进行预处理,然后使用开阔地(OF)测试评估运动活动,并使用体内固定电位安培计评估多巴胺的阶段性释放。长期暴露于AA-5-HT不会改变运动活动或多巴胺间叶功能。长期暴露于乙酰乙酰乙酰胆碱酯酶会降低小鼠的饲养能力并减少阶段性多巴胺释放,同时增加小鼠对可卡因的多巴胺能反应。在实验2中,小鼠接受了AA-5-HT、ACEA或载体的条件性位置偏好测试,然后又接受了糖精偏好测试,这是一种通常与失乐症相关的测量方法。小鼠对AA-5-HT或ACEA没有产生条件性位置偏好或厌恶,重复暴露于AA-5-HT或ACEA也没有改变对糖精的偏好。总之,研究结果表明,这两种药物都不会诱导小鼠产生与滥用相关的行为;不过,与间接大麻素激动作用相比,直接大麻素受体 1 型激动作用可能在介导间叶多巴胺功能方面发挥更大的作用。(PsycInfo Database Record (c) 2024 APA,保留所有权利)。
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Behavioral neuroscience
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