Pharmacology Biochemistry and Behavior最新文献_第2页

Purified cannabidiol leads to improvement of severe treatment-resistant behavioral symptoms in children with autism spectrum disorder

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-16 DOI: 10.1016/j.pbb.2025.173971

Pablo Sebastián Fortini , Javier J. Toibaro , Roberto H. Caraballo

Objective

The aim of our study was to evaluate the efficacy and safety of purified cannabidiol as an add-on medication in pediatric patients with autism spectrum disorder (ASD) associated with treatment resistant repetitive behaviors, behavior disorders, and intellectual disability and unresponsive to conventional medications and behavioral interventions.

Material and methods

A prospective, observational, before-and-after study was conducted including 20 patients with severe ASD who initiated treatment with purified CBD. Patients were evaluated using different scales at baseline and at three-month intervals during followup.

Results

The median total CBD dose was 363.5 mg (range, 100–700), and the median follow-up was 11 months (range, 6–12). As to the primary outcome evaluating symptoms reported by parents, improvement in at least one was observed after CBD initiation in 18 patients (90 %) and no improvement in two (10 %) (1 worsening, 1 no response). In the responders, 83.5 % (n = 76) of all reported symptoms improved. Regarding the secondary outcomes based on the assessment with different scales, improvement of around 30 % was found in irritability, social withdrawal, hyperactivity. Restricted and repetitive behavior improved in nine (50 %), while no changes were seen in seven (38.8 %). Sleep patterns were found to be slightly improved. Adverse effects were reported in 13 patients (65 %), mainly consisting of increased irritability and decreased appetite, but were mild or moderate and transient in all. In 40 % of the children, concomitant medication could be reduced or partially discontinued.

Conclusion

Our results suggest that treatment with purified CBD is effective and safe and could benefit patients with severe ASD by improving some of the core symptoms, including repetitive behaviors and social interaction, as well as associated comorbidities. The families considered the quality of life to have improved.

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引用次数: 0

Striatal dopamine D2, adenosine A2A and cannabinoid CB1 receptors balance as a target against non-cognitive symptoms in a mouse model of Alzheimer's disease

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-14 DOI: 10.1016/j.pbb.2025.173970

Laura Gómez-Acero , Nuria Sánchez-Fernández , Paula Subirana , Francisco Ciruela , Ester Aso

Behavioral and psychological symptoms of dementia are almost ubiquitous in Alzheimer's disease (AD) but current therapies are not fully effective and safe. In this study, we aim to evaluate the role played by the interplay among striatal D₂, adenosine A_2A (A_2AR) and cannabinoid CB₁ (CB₁R) receptors in some of these non-cognitive impairments in a well-established animal model of AD, the double transgenic APP/PS1 mice. Our results reveal that the alterations existing in the ratios between these three receptors significantly correlate with the sensorimotor gating and the social interaction impairments occurring in APP/PS1 mice at 12 months of age. Moreover, the pharmacological stimulation of A_2AR and CB₁R blunted the sensorimotor gating deficiencies in APP/PS1 mice. To note, we observed some age-dependent differences among male and female mice. In conclusion, the present study provides evidence for the contribution of an altered interplay between dopaminergic, adenosinergic and endocannabinoid systems in the sensorimotor gating deficits and social withdrawal occurring in AD and points to A_2AR and CB₁R as a potential target to reverse these non-cognitive symptoms in AD patients.

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引用次数: 0

Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-06 DOI: 10.1016/j.pbb.2025.173969

Daniel Bussinger de Souza Penna , Samara Gumiéro Costa , Juliana Santos Romão , Karin da Costa Calaza , Karen de Jesus Oliveira , Alexandre dos Santos Rodrigues , Pablo Pandolfo

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting individuals across age groups. Impairments in executive function characterize ADHD and are often associated with elevated levels of risk-taking behaviors. The endocannabinoid system plays a crucial role in modulating prefrontal cortex circuits. Here, we assessed the effects of acute pharmacological manipulation of cannabinoid CB1 and CB2 receptors on locomotion and risk assessment/anxiety-like behaviors in an ADHD animal model during adolescence and adulthood. Further, we investigated the protein levels and gene expression of endocannabinoid system components (CB1, CB2, FAAH, MAGL) in the prefrontal cortex at both ages. During adolescence, activation of cannabinoid receptors aggravated the hyperactivity and risky behaviors of the ADHD model. These behavioral traits were more evident in female rats. In adulthood, manipulation of cannabinoid receptors did not alter hyperactivity but worsened risk assessment. Overall, gene expression levels of receptors and enzymes of the endocannabinoid system were increased in the ADHD model. Our findings suggest that the endocannabinoid system may operate differently in ADHD, and manipulating this system, especially in adolescents, could exacerbate deficits in inhibitory control.

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引用次数: 0

Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-04 DOI: 10.1016/j.pbb.2025.173968

Ariana C. Brice-Tutt , Niall P. Murphy , Barry Setlow , Alexandria S. Senetra , Wendi Malphurs , Robert M. Caudle , Adriaan W. Bruijnzeel , Marcelo Febo , Abhisheak Sharma , John K. Neubert

Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain. Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration. To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward. All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements - which too was magnified by co-administration of cannabidiol. Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.

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引用次数: 0

Combination treatment with rapamycin and glucocorticoid protects the death of mesostriatal dopaminergic neurons in animal model of Parkinson's disease

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-03 DOI: 10.1016/j.pbb.2025.173966

Kina Lee , Hee Jeong Kim , Jeong Eun Kim , K.C. Elina , Sangjune Kim , Young Seok Park , Hyong Kyu Kim

Glucocorticoids have been used to treat inflammatory diseases because of their potent anti-inflammatory and immunosuppressive actions. However, chronic use of high levels of glucocorticoids causes several adverse effects, limiting their clinical utility. Here, we explored the therapeutic potential of a combination treatment involving reduced concentrations of rapamycin, an autophagy activator and immunosuppressant, and glucocorticoids in an animal model of Parkinson's disease (PD). In vitro experiments with the SH-SY5Y cell line revealed that 10 μM rapamycin significantly increased the survival rate of cells treated with 6-hydroxydopamine to induce cell death, while both dexamethasone and prednisone at 50 μM exhibited an evident increase in survival rates. The combination treatment with reduced concentrations (rapamycin: 5 μM, dexamethasone: 25 μM) showed a more effective recovery in survival than singular treatments with high concentrations of rapamycin, prednisone, or dexamethasone. Propidium iodide–staining confirmed the efficacy of the combination treatment. This treatment did not significantly alter forkhead box O3a (FOXO3a)–triggered apoptosis and autophagic flux but upregulated the expression of the anti-apoptotic protein B-cell lymphoma 2, while B-cell lymphoma–extra-large showed no significant change. In vivo experiments using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced PD animal model revealed that the combination treatment effectively mitigated defects in motor function. The combination treatment completely blocked the loss of tyrosine hydroxylase (TH)–positive neurons in the substantia nigra pars compacta and partially prevented the reduction of TH-positive fibers in the striatum caused by the MPTP treatment. It also reduced the microglial levels caused by the MPTP treatment. Although not significant, it demonstrated an increase in survival rates of MPTP-induced PD model mice. In conclusion, the combination treatment with reduced concentrations of rapamycin and glucocorticoids may serve as potential therapy for PD, albeit further research and clinical trials are warranted to validate its efficacy and safety.

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引用次数: 0

GW117 induces anxiolytic effects by improving hippocampal functions GW117通过改善海马功能诱导抗焦虑作用。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173927

Ya-qi Yang , Murezati Tiliwaerde , Na-na Gao , Wei Gu , Ting-ting Zhang , Zeng-liang Jin

GW117 functions as both an MT1/MT2 receptor agonist and a 5-HT2C receptor antagonist. This study aimed to investigate the anxiolytic effects of GW117 through behavioral assessments, including the open field test and novelty-suppressed feeding test (NSFT) within a chronic unpredictable mild stress (CUMS) model. GW117 was administered via oral gavage for 21 days to evaluate its sustained anxiolytic effects, with behavioral tests including the NSFT, the Vogel-conflict test, and the O-maze test. To explore the underlying mechanisms, we performed Western blot analyses to assess the expression levels of BCL2-Associated X (Bax), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). Additionally, BrdU labeling and immunofluorescence staining were used to examine changes in neuronal regeneration and astrocytogenesis. Our results demonstrated that GW117 produced significant anxiolytic effects across all behavioral assays, both in the CUMS model and during long-term administration. Mechanistic studies revealed that GW117 notably increased the expression of BDNF, GFAP, and Bcl-2, while reducing Bax and cleaved caspase-3 levels in the hippocampus of CUMS model rats. Furthermore, the populations of BrdU-positive and GFAP-positive cells were elevated. These findings suggest that GW117 exerts anxiolytic effects, potentially through enhancements in hippocampal function.

GW117同时作为MT1/MT2受体激动剂和5-HT2C受体拮抗剂。本研究旨在通过行为评估研究GW117的抗焦虑作用，包括在慢性不可预测轻度应激（CUMS）模型中进行开放场试验和新奇性抑制喂养试验（NSFT）。GW117口服灌胃21 天，评估其持续抗焦虑作用，并进行行为测试，包括NSFT、vogel冲突测试和o型迷宫测试。为了探索潜在的机制，我们进行了Western blot分析，以评估BCL2-Associated X （Bax）、cleaved caspase-3、b细胞淋巴瘤-2 （Bcl-2）、脑源性神经营养因子（BDNF）和胶质纤维酸性蛋白（GFAP）的表达水平。此外，BrdU标记和免疫荧光染色检测神经元再生和星形细胞发生的变化。我们的研究结果表明，GW117在所有行为分析中都产生了显著的抗焦虑作用，无论是在CUMS模型中还是在长期给药过程中。机制研究显示，GW117显著增加了CUMS模型大鼠海马中BDNF、GFAP和Bcl-2的表达，同时降低了Bax和cleaved caspase-3的表达。此外，brdu阳性和gfap阳性细胞的数量也有所增加。这些发现表明，GW117可能通过增强海马功能发挥抗焦虑作用。

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引用次数: 0

Caffeic acid differentially modulates behavior and neurochemicals in chronic unpredictable mild stress and dexamethasone induced models of depression 咖啡酸在慢性不可预测的轻度应激和地塞米松诱导的抑郁症模型中差异调节行为和神经化学物质。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173930

Hariom, Prerna Kumari, Sushma Chaturvedi, Sonika Shrivastav, Sushma Maratha, Vaibhav Walia

In the present study authors studied the effect of caffeic acid (CA) in chronic unpredictable mild stress (CUMS) and dexamethasone (DEXA) model of depression. CUMS (21 days) and DEXA (1.5 mg/kg × 21 days) was used for the induction of depression and anxiety related behavior. Locomotor activity was determined using actophotometer. Depression related behavior was determined using tail suspension test (TST) and forced swim test (FST) whereas for the determination of anxiety related behavior elevated plus maze (EPM) test was used. Following behavioral studies, mice were sacrificed by decapitation method. Hippocampus was dissected and was used for the neurochemical assays including 5-HT (serotonin), glutamate, nitrite and gamma-aminobutyric acid (GABA). The results obtained suggested that the CA (25–100 mg/kg, i.p.) did not affect the activity count in CUMS exposed and DEXA treated mice. CA (50 mg/kg) evoked anxiogenic reactions in CUMS model by increasing the hippocampal nitrite and glutamate level while CA (50 mg/kg) exerted anxiolysis in DEXA model by reducing the level of 5-HT. In CUMS model, CA exerted antidepressant like effect by increasing the hippocampal nitric oxide (NO) level, in DEXA model CA exerted antidepressant like effect by reducing the hippocampal glutamate level. CA failed to reverse DEXA mediated nNOS inhibition and therefore decreases hippocampal glutamate level to exert antidepressant like effect. Thus, CA modulate anxiety and depression related neurobehavioral alterations in both CUMS and DEXA models.

本研究探讨了咖啡酸（CA）在慢性不可预测轻度应激（CUMS）和地塞米松（DEXA）抑郁症模型中的作用。采用CUMS（21 d）和DEXA（1.5 mg/kg × 21 d）诱导抑郁和焦虑相关行为。运动活动测定采用光热计。抑郁相关行为采用悬尾测试（TST）和强迫游泳测试（FST），焦虑相关行为采用升高迷宫测试（EPM）。行为学研究后，采用断头法处死小鼠。解剖海马，进行5-羟色胺（5-羟色胺）、谷氨酸、亚硝酸盐和γ -氨基丁酸（GABA）的神经化学检测。结果表明，CA（25-100 mg/kg, i.p.）对CUMS暴露和DEXA处理小鼠的活性计数没有影响。CA（50 mg/kg）通过增加海马亚硝酸盐和谷氨酸水平引起CUMS模型的焦虑反应，CA（50 mg/kg）通过降低5-HT水平引起DEXA模型的焦虑反应。在CUMS模型中，CA通过提高海马一氧化氮（NO）水平发挥抗抑郁样作用；在DEXA模型中，CA通过降低海马谷氨酸水平发挥抗抑郁样作用。CA未能逆转DEXA介导的nNOS抑制，从而降低海马谷氨酸水平，发挥类似抗抑郁药的作用。因此，在CUMS和DEXA模型中，CA调节焦虑和抑郁相关的神经行为改变。

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引用次数: 0

Early adolescent second-generation antipsychotic exposure produces long-term, post-treatment increases in body weight and metabolism-associated gene expression 青少年早期服用第二代抗精神病药物会产生长期的、治疗后的体重和代谢相关基因表达增加。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173951

Paul L. Soto , Michael E. Young , Serena Nguyen , Megan Federoff , Mia Goodson , Christopher D. Morrison , Heidi M. Batdorf , Susan J. Burke , J. Jason Collier

The use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. High-fat diet feeding did not produce a robust difference in weight gain in previously treated vs. control groups. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.

在儿科患者中使用第二代抗精神病药物（SGA）引起了对潜在长期不良后果的担忧。目前的研究评估了利培酮或奥氮平治疗对C57Bl/6J雌性小鼠体重、热量摄入、血清胰岛素、血糖和代谢相关基因表达的长期影响。与对照组相比，接受利培酮或奥氮平治疗的雌性小鼠在治疗期间体重增加的速度更快，并且在停止治疗后的几个月内保持较高的体重。在喂食高脂肪食物的过程中，一些实验组的老鼠体重增加的速度比它们各自的对照组要快，但这一发现在不同的实验中并不一致。最后，先前用奥氮平治疗的雌性小鼠也表现出与炎症和脂肪生成相关的基因表达增加。这些发现表明，儿童在治疗期间使用SGA药物会导致体重过度增加，这可能会对体重和基因表达产生持续影响，这些结果可能会成为评估处方决策风险-收益比的一个重要方面。

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引用次数: 0

Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice 急性大麻二酚治疗逆转雄性小鼠胚胎丙戊酸暴露引起的行为障碍。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173919

J.F.C. Pedrazzi , A.J. Sales , R.S.M. Ponciano , L.G. Ferreira , F.R. Ferreira , A.C. Campos , J.E.C. Hallak , A.W. Zuardi , E.A. Del Bel , F.S. Guimarães , J.A. Crippa

Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD). This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects. Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12^° day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials. In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group. These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder.

大麻二酚（CBD）是大麻植物中主要的非精神类化合物，在治疗自闭症谱系障碍（ASD）相关的各种症状方面显示出良好的效果。这种神经发育障碍通常影响认知、行为、社会沟通和运动技能领域。然而，对与该疾病相关的广泛症状的有效治疗是有限的，并且可能引发不良影响。啮齿类动物胚胎暴露于丙戊酸（VPA， 12°d时500 mg/kg）是研究ASD相关行为和分子特征的综合环境模型。因此，本研究旨在通过四个不同的试验来评估急性CBD是否可以逆转胚胎期暴露于VPA的成年小鼠（8周）的行为障碍。在独立的动物群体中，进行了以下测试：I)脉冲前抑制测试（PPI）， II)大理石掩埋，III)社会互动，IV)活度计测试，V)新目标识别测试（NOR）。在PPI模式中，暴露于VPA的小鼠表现出PPI损伤，CBD（30和60 mg/kg）逆转了这种破坏。CBD（60 mg/kg）分别减少了埋弹珠的数量，提高了社交互动时间，但未能减少VPA组的刻板动作。在NOR试验中，两种剂量的CBD均可逆转VPA组诱导的识别指数损伤。这些发现表明，在研究这种神经发育障碍的成熟动物模型中，急性给药CBD可以改善与ASD相关的行为障碍。

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引用次数: 0

Reconsidering OCD pharmacotherapy: The case for levomilnacipran as a safer alternative to clomipramine 重新考虑强迫症药物治疗：左旋美那西普兰作为氯丙咪嗪更安全的替代品。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173942

Luke Manietta

引用次数: 0