Psychopharmacology最新文献

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Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance 在阿片类药物维持治疗大鼠模型中,长期给药 NOP/MOR 部分激动剂 AT-201 和 NOP 拮抗剂 J-113397 对海洛因复吸的影响
IF 3.4 3区 医学
Psychopharmacology Pub Date : 2024-09-13 DOI: 10.1007/s00213-024-06678-7
Jennifer M. Bossert, Kiera E. Caldwell, Hannah Korah, Ashley Batista, Hannah Bonbrest, Ida Fredriksson, Shelley N. Jackson, Agnieszka Sulima, Kenner C. Rice, Nurulain T. Zaveri, Yavin Shaham
{"title":"Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance","authors":"Jennifer M. Bossert, Kiera E. Caldwell, Hannah Korah, Ashley Batista, Hannah Bonbrest, Ida Fredriksson, Shelley N. Jackson, Agnieszka Sulima, Kenner C. Rice, Nurulain T. Zaveri, Yavin Shaham","doi":"10.1007/s00213-024-06678-7","DOIUrl":"https://doi.org/10.1007/s00213-024-06678-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>The opioid crisis persists despite availability of effective opioid agonist maintenance treatments (methadone and buprenorphine). Thus, there is a need to advance novel medications for the treatment of opioid use and relapse.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We recently modeled maintenance treatment in rats and found that chronic delivery of buprenorphine and the mu opioid receptor (MOR) partial agonist TRV130 decreases relapse to oxycodone seeking and taking. In contrast, chronic delivery of the buprenorphine analog BU08028 had mixed effects on different heroin relapse-related measures. Here, we tested the effect of the mixed nociceptin (NOP) receptor/MOR partial agonist AT-201 and the NOP receptor antagonist J-113397 on different heroin relapse-related measures.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We trained male and female rats to self-administer heroin (6-h/d, 14-d) in context A and then implanted osmotic minipumps containing AT-201 (0, 3.8, or 12 mg/kg/d) or J-113397 (0, 12.6, or 40 mg/kg/d). Next, we tested the effect of chronic delivery of the compounds on (1) incubation of heroin seeking in a non-drug context B, (2) extinction responding reinforced by heroin-associated discrete cues in context B, (3) context A-induced reinstatement of heroin seeking, and (4) reacquisition of heroin self-administration in context A.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In females, AT-201 modestly <i>increased</i> reacquisition of heroin self-administration and J-113397 modestly <i>decreased</i> incubation of heroin seeking. The compounds had no effect on the other relapse-related measures in females, and no effect on any of the measures in males.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The NOP/MOR partial agonist AT-201 and the NOP antagonist J-113397 did not mimic buprenorphine’s inhibitory effects on relapse in a rat model of opioid maintenance treatment.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: therapeutic target for CNS disorders 大麻素受体 CB2 受体在中枢神经系统中的新作用:中枢神经系统疾病的治疗靶点
IF 3.4 3区 医学
Psychopharmacology Pub Date : 2024-09-12 DOI: 10.1007/s00213-024-06683-w
Kanchan Bala, Pratyush Porel, Khadga Raj Aran
{"title":"Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: therapeutic target for CNS disorders","authors":"Kanchan Bala, Pratyush Porel, Khadga Raj Aran","doi":"10.1007/s00213-024-06683-w","DOIUrl":"https://doi.org/10.1007/s00213-024-06683-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Rationale</h3><p>The endocannabinoid system (ECS) belongs to the G protein-coupled receptor family of cell membranes and is associated with neuropsychiatric conditions, and neurodegenerative diseases. Cannabinoid 2 receptors (CB2) are expressed in the central nervous system (CNS) on microglia and subgroups of neurons and are involved in various behavioural processes via immunological and neural regulation.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The objective of this paper is to summarize and explore the impact of CB2 receptors on neuronal modulation, their involvement in various neurological disorders, and their influence on mood, behavior, and cognitive function.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The activation of CB2 appears to protect the brain and its functions from damage under neuroinflammatory actions, making it an attractive target in a variety of neurological conditions such as Parkinson’s disease (PD), multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington’s disease (HD). During inflammation, there is an overexpression of CB2 receptors, and CB2 agonists show a strong anti-inflammatory effect. These results have sparked interest in the CB2 receptors as a potential target for neurodegenerative and neuroinflammatory disease treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In conclusion, CB2 receptors signalling shows promise for developing targeted interventions that could positively affect both immune and neuronal functions, ultimately influencing behavioral outcomes in both health and disease.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal 阐明分子交响乐:解开阿片类药物依赖和戒断中神经可塑性的转录和表观遗传途径
IF 3.4 3区 医学
Psychopharmacology Pub Date : 2024-09-10 DOI: 10.1007/s00213-024-06684-9
Shahid Nazir Wani, Amarjot Kaur Grewal, Heena Khan, Thakur Gurjeet Singh
{"title":"Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal","authors":"Shahid Nazir Wani, Amarjot Kaur Grewal, Heena Khan, Thakur Gurjeet Singh","doi":"10.1007/s00213-024-06684-9","DOIUrl":"https://doi.org/10.1007/s00213-024-06684-9","url":null,"abstract":"<p>The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of agomelatine on sleep disorders and lateral habenula neuronal activity in chronic restraint stress depression model mice. 阿戈美拉汀对慢性束缚应激抑郁模型小鼠睡眠障碍和外侧哈文神经元活动的疗效
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-09 DOI: 10.1007/s00213-024-06681-y
Zhuojun Kang, Zhenzhen Zheng, Wenli Guo
{"title":"Efficacy of agomelatine on sleep disorders and lateral habenula neuronal activity in chronic restraint stress depression model mice.","authors":"Zhuojun Kang, Zhenzhen Zheng, Wenli Guo","doi":"10.1007/s00213-024-06681-y","DOIUrl":"https://doi.org/10.1007/s00213-024-06681-y","url":null,"abstract":"<p><strong>Background: </strong>Sleep disorders (SD) are one of the common manifestations of depression patients. This article aimed to explore the effect of Agomelatine (Ago) on SD in chronic restraint stress (CRS) depression model mice and its effect on the activity of neurons in the lateral habenula (LHb).</p><p><strong>Methods: </strong>30 C57BL/6 J mice were divided into normal (C57BL/6 J) group, CRS group, and Ago group. CRS experiment was used to establish the depression model, and Ago was used to treat CRS mice. Based on behavioral tests in mice and electrophysiology record, SD and LHb neuron activity were assessed. The expression levels of brain-derived neurotrophic factor (BDNF) and nuclear phosphoprotein (c-Fos) in LHb were detected by Western blot (WB).</p><p><strong>Results: </strong>As against the CRS group, the Ago group had a reduction in the immobility time during forced swimming training and an increase in the preference for sucrose in the sucrose preference test; The expression levels of c-Fos and BDNF proteins in the LHb neurons of the Ago group mice were lower than those in the CRS group (P < 0.05), and the values approached the levels of the normal control group. In both dark and light environments, the rapid eye movement (REM) sleep duration of the CRS group mice was significantly longer than that of the normal control group (P < 0.05).</p><p><strong>Conclusion: </strong>It was concluded that Ago may intervene in the depressive-like behavior and overall sleep patterns of CRS depression model mice by regulating the activity of LHb neurons and inhibiting the neuroinflammatory process. This provides a potential drug target for the development of new treatment strategies for depression.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide. 麦角酰二乙胺急性和持续微剂量使用后的多模式创造力评估。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-05 DOI: 10.1007/s00213-024-06680-z
Robin J Murphy, Rachael L Sumner, Kate Godfrey, Acima Mabidikama, Reece P Roberts, Frederick Sundram, Suresh Muthukumaraswamy
{"title":"Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide.","authors":"Robin J Murphy, Rachael L Sumner, Kate Godfrey, Acima Mabidikama, Reece P Roberts, Frederick Sundram, Suresh Muthukumaraswamy","doi":"10.1007/s00213-024-06680-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06680-z","url":null,"abstract":"<p><strong>Introduction: </strong>Enhanced creativity is often cited as an effect of microdosing (taking repeated low doses of a psychedelic drug). There have been recent efforts to validate the reported effects of microdosing, however creativity remains a difficult construct to quantify.</p><p><strong>Objectives: </strong>The current study aimed to assess microdosing's effects on creativity using a multimodal battery of tests as part of a randomised controlled trial of microdosing lysergic acid diethylamide (LSD).</p><p><strong>Methods: </strong>Eighty healthy adult males were given 10 µg doses of LSD or placebo every third day for six weeks (14 total doses). Creativity tasks were administered at a drug-free baseline session, at a first dosing session during the acute phase of the drug's effects, and in a drug-free final session following the six-week microdosing regimen. Creativity tasks were the Alternate Uses Test (AUT), Remote Associates Task (RAT), Consensual Assessment Technique (CAT), and an Everyday Problem-Solving Questionnaire (EPSQ).</p><p><strong>Results: </strong>No effect of drug by time was found on the AUT, RAT, CAT, or EPSQ. Baseline vocabulary skill had a significant effect on AUT and RAT scores.</p><p><strong>Conclusions: </strong>Despite participants reporting feeling more creative on dose days, objective measurement found no acute or durable effects of the microdosing protocol on creativity. Possible explanations of these null findings are that laboratory testing conditions may negatively affect ability to detect naturalistic differences in creative performance, the tests available do not capture the facets of creativity that are anecdotally affected by microdosing, or that reported enhancements of creativity are placebo effects.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Obituary Dr Klaus A Miczek 讣告 Klaus A Miczek 博士
IF 3.4 3区 医学
Psychopharmacology Pub Date : 2024-09-04 DOI: 10.1007/s00213-024-06677-8
Harriet de Wit, T. W. Robbins
{"title":"Obituary Dr Klaus A Miczek","authors":"Harriet de Wit, T. W. Robbins","doi":"10.1007/s00213-024-06677-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06677-8","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks. 劳拉西泮对回旋眼球运动的影响--来自前注视和自由注视任务的证据。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-03 DOI: 10.1007/s00213-024-06672-z
Philine M Baumert, Kaja Faßbender, Maximilian W M Wintergerst, Jan H Terheyden, Behrem Aslan, Tom Foulsham, Wolf Harmening, Ulrich Ettinger
{"title":"Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.","authors":"Philine M Baumert, Kaja Faßbender, Maximilian W M Wintergerst, Jan H Terheyden, Behrem Aslan, Tom Foulsham, Wolf Harmening, Ulrich Ettinger","doi":"10.1007/s00213-024-06672-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06672-z","url":null,"abstract":"<p><strong>Rationale: </strong>Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks.</p><p><strong>Objectives: </strong>The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions.</p><p><strong>Methods: </strong>1 mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task.</p><p><strong>Results: </strong>Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam.</p><p><strong>Conclusions: </strong>Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis. 成人和儿童精神病住院患者丙戊酸稳态血清水平的预测因素:对比分析。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-01 Epub Date: 2024-05-11 DOI: 10.1007/s00213-024-06603-y
Matan Avrahami, Timur Liwinski, Zafrir Eckstein, Miriam Peskin, Polina Perlman, Jan Sarlon, Undine E Lang, Daniela Amital, Abraham Weizman
{"title":"Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.","authors":"Matan Avrahami, Timur Liwinski, Zafrir Eckstein, Miriam Peskin, Polina Perlman, Jan Sarlon, Undine E Lang, Daniela Amital, Abraham Weizman","doi":"10.1007/s00213-024-06603-y","DOIUrl":"10.1007/s00213-024-06603-y","url":null,"abstract":"<p><strong>Rationale: </strong>Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined.</p><p><strong>Objectives: </strong>To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients.</p><p><strong>Methods: </strong>We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors.</p><p><strong>Results: </strong>Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (β = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (β = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction.</p><p><strong>Conclusions: </strong>This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Heterogeneity in choice models of addiction: the role of context. 成瘾选择模型中的异质性:背景的作用。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-01 Epub Date: 2024-07-11 DOI: 10.1007/s00213-024-06646-1
Samuel F Acuff, Justin C Strickland, Kirsten Smith, Matt Field
{"title":"Heterogeneity in choice models of addiction: the role of context.","authors":"Samuel F Acuff, Justin C Strickland, Kirsten Smith, Matt Field","doi":"10.1007/s00213-024-06646-1","DOIUrl":"10.1007/s00213-024-06646-1","url":null,"abstract":"<p><strong>Rationale: </strong>Theories of addiction guide scientific progress, funding priorities, and policy development and ultimately shape how people experiencing or recovering from addiction are perceived and treated. Choice theories of addiction are heterogenous, and different models have divergent implications. This breeds confusion among laypeople, scientists, practitioners, and policymakers and reduces the utility of robust findings that have the potential to reduce the global burden of addiction-associated harms.</p><p><strong>Objective: </strong>Here we differentiate classes of choice models and articulate a novel framing for a class of addiction models, called contextual models, which share as a first principle the influence of the environment and other contextual factors on behavior within discrete choice contexts.</p><p><strong>Results: </strong>These models do not assume that all choice behaviors are voluntary, but instead that both proximal and distal characteristics of the choice environment-and particularly the benefits and costs of both drug use and non-drug alternatives-can influence behavior in ways that are outside of the awareness of the individual. From this perspective, addiction is neither the individual's moral failing nor an internal uncontrollable urge but rather is the result of environmental contingencies that reinforce the behavior.</p><p><strong>Conclusions: </strong>Contextual models have implications for guiding research, practice, and policy, including identification of novel target mechanisms while also improving existing interventions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model. 在雌二醇戒断模型中通过上调BDNF和β-catenin激活下边缘皮层的抗抑郁作用
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-09-01 Epub Date: 2024-05-14 DOI: 10.1007/s00213-024-06610-z
Jiali Chen, Yiying Zhou, Miaojun Lai, Yanping Zhang, Yifang Hu, Dingding Zhuang, Wenhua Zhou, Yisheng Zhang
{"title":"Antidepressant effects of activation of infralimbic cortex via upregulation of BDNF and β-catenin in an estradiol withdrawal model.","authors":"Jiali Chen, Yiying Zhou, Miaojun Lai, Yanping Zhang, Yifang Hu, Dingding Zhuang, Wenhua Zhou, Yisheng Zhang","doi":"10.1007/s00213-024-06610-z","DOIUrl":"10.1007/s00213-024-06610-z","url":null,"abstract":"<p><strong>Rationale: </strong>Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear.</p><p><strong>Objectives: </strong>This study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD.</p><p><strong>Methods: </strong>Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting.</p><p><strong>Results: </strong>Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats.</p><p><strong>Conclusions: </strong>Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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