Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist.

IF 1.6 4区心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2023-06-01 DOI:10.1097/FBP.0000000000000720

Farahnaz Taheri, Khadijeh Esmaeilpour, Gholamreza Sepehri, Vahid Sheibani, Majid Asadi Shekari

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Abstract

Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48-50 (PND 48-50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48-50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups.

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组胺h3受体拮抗剂环丙昔芬改善丙戊酸诱导的自闭症动物模型的认知障碍

自闭症谱系障碍是一种以社会沟通缺陷和重复行为为特征的神经发育障碍。许多研究表明，组胺H3受体(H3R)拮抗剂可以减少认知障碍的数量。本研究在出生后48-50天(PND 48-50)，采用埋弹任务(MBT)、开阔场地、新目标识别(NOR)和被动回避任务，研究了环丙西芬(CPX)(1和3 mg/kg，腹腔注射)对丙戊酸(VPA) (600 mg/kg，腹腔注射)暴露大鼠幼崽认知障碍的影响。法莫替丁(FAM)(10、20和40 mg/kg，腹腔注射)也被用来确定组胺能神经传递是否通过H2受体(H2Rs)发挥其促进认知的作用。此外，通过组织学检查评估海马神经元的退化程度。结果显示，暴露于vpa的大鼠后代在MBT中重复行为增加。此外，暴露于vpa的大鼠后代在野外表现出比盐处理大鼠更多的焦虑样行为。研究发现，暴露于vpa的大鼠后代在NOR和被动回避任务中表现出记忆缺陷。结果表明，3mg /kg CPX可改善VPA诱导的认知障碍，而20mg /kg FAM可减轻VPA诱导的认知障碍。我们得出结论，3mg /kg CPX通过H3Rs改善vpa诱导的认知障碍。组织学评估显示，与盐暴露的大鼠后代相比，vpa暴露的大鼠后代的CA1神经元数量减少，但这种减少并不显著。组织学评估也显示，与盐暴露大鼠后代相比，vpa暴露大鼠后代的CA1神经元没有显著差异。然而，与VPA +生理盐水组相比，CPX3使VPA + CPX3组CA1神经元数量增加，但这种增加并不显著。本研究表明，暴露于VPA的大鼠在MBT、open field、NOR和被动回避测试中表现出认知障碍，CPX在PND 48-50上治疗后，这些障碍得到改善。此外，形态学研究表明，VPA处理未导致大鼠海马CA1亚区神经元变性。

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来源期刊

Behavioural Pharmacology 医学-行为科学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.