Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Panepistimiou 3, 415-00, Larissa, Greece.
Department of Pharmacology, School of Medicine, and Institute of Molecular Biology & Biotechnology, Foundation of Research & Technology-Hellas, University of Crete, Heraklion, Greece.
Psychopharmacology (Berl). 2021 Jan;238(1):227-237. doi: 10.1007/s00213-020-05672-z. Epub 2020 Oct 2.
Schizophrenia is a devastating mental disease that affects nearly 1% of the population worldwide. It is well documented that the dopaminergic (DAergic) system is compromised in schizophrenia. It is of note that the mixed dopamine (DA) D/D receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Neuroactive steroids, comprising dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS), were shown to affect brain DAergic system and to be involved in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. It has recently been reported that BNN27 counteracted schizophrenia-like behavioural deficits produced by glutamate hypofunction in rats.
The aim of the present study was to investigate the ability of BNN27 to attenuate non-spatial, spatial recognition and discrete memory deficits induced by apomorphine in rats.
To this end, the object recognition task (ORT), the object location task (OLT) and the step-through passive avoidance test (STPAT) were used.
BNN27 (3 and 6 mg/kg, i.p.) attenuated apomorphine (0.5 mg/kg, i.p.)-induced non-spatial, spatial recognition and discrete memory deficits. Interestingly, the effects of compounds on memory cannot be ascribed to changes in locomotor activity.
Our findings suggest that BNN27 is effective to DA dysfunction caused by apomorphine, attenuating cognitive impairments induced by this D1/D2 receptor agonist in rats. Additionally, our findings illustrate a functional interaction between BNN27 and the DAergic system that may be of relevance for schizophrenia-like behavioural symptoms.
精神分裂症是一种严重的精神疾病，全球近 1%的人口受其影响。多巴胺能（DAergic）系统在精神分裂症中受损已有充分的文献记载。值得注意的是，混合多巴胺（DA）D/D 受体激动剂阿朴吗啡会在啮齿动物中引起类似精神分裂症的症状，包括记忆能力受损。神经活性甾体包括脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS），它们被证明会影响大脑的 DA 能系统，并与精神分裂症有关。BNN27 是一种新的 DHEA 衍生物，没有甾体生成活性。最近有报道称，BNN27 可对抗谷氨酸功能低下引起的大鼠类似精神分裂症的行为缺陷。
本研究旨在研究 BNN27 减轻阿朴吗啡诱导的大鼠非空间、空间识别和离散记忆缺陷的能力。
为此，使用了物体识别任务（ORT）、物体位置任务（OLT）和穿梭式被动回避测试（STPAT）。
BNN27（3 和 6mg/kg，腹腔注射）减轻了阿朴吗啡（0.5mg/kg，腹腔注射）诱导的非空间、空间识别和离散记忆缺陷。有趣的是，化合物对记忆的影响不能归因于运动活动的变化。
我们的发现表明，BNN27 对阿朴吗啡引起的 DA 功能障碍有效，可减轻这种 D1/D2 受体激动剂诱导的大鼠认知障碍。此外，我们的发现说明了 BNN27 与 DA 能系统之间的功能相互作用，这可能与类似精神分裂症的行为症状有关。
