The nitric oxide (No) donor sodium nitroprusside (snp) and its potential for the schizophrenia therapy: Lights and shadows

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide popula-tion. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra‐ and inter‐cellular messenger in the brain, appears to be implicated in the patho-genesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medi-cation of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts cognitive deficits induced by the D1/D2 dopaminergic receptor agonist apomorphine in rats

Rationale: 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) D1/D2 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. Objectives: 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. Methods: To this end, the object recognition task (ORT), the object location task (OLT) and the step-through passive avoidance test (STPAT) were used. Results: 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. Conclusions: 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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

The novel dehydroepiandrosterone derivative BNN27 counteracts the impairing effects of anesthetic ketamine on rats’ non-spatial and spatial recognition memory

Conspicuous experimental evidence indicates that anesthetic doses of the non-competitive NMDA receptor antagonist ketamine disrupt memory abilities in rodents. BNN27 is a synthetic analogue of dehydroepiandrosterone (DHEA) with potent antioxidant properties and its involvement in cognition has recently been shown. It is not yet clarified whether BNN27 can attenuate the cognition deficits induced by anesthetic ketamine. The present study was designed to elucidate this issue in the rat. For this purpose, the object recognition and the object location tests which are behavioral procedures evaluating non-spatial and spatial recognition memory respectively in rodents were used. The effects of compounds on motility were also tested utilizing a motor activity cage. Post-training administration of BNN27 (3 and 6 mg/kg, intraperitoneally) counteracted anesthetic ketamine (100 mg/kg, intraperitoneally)-induced non-spatial and spatial recognition memory deficits. Further, these effects cannot be attributed to changes to locomotor activity. Our findings clearly show the protective role of BNN27, on recognition memory impairment induced by anesthetic ketamine, indicating a functional interaction following co-administration of synthetic microneurotrophins and ketamine. © 2022 Elsevier B.V

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts behavioural deficits induced by the NMDA receptor antagonist ketamine in rats

Consistent experimental evidence supports an important role of the glutamatergic system in the etiopathogenesis of schizophrenia. Numerous studies propose that blockade of the NMDA receptor by its antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Neuroactive steroids, including dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were shown to affect brain glutamatergic system and to be implicated in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently evidenced. The aim of the present study was to investigate the ability of BNN27 to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. BNN27's ability to attenuate hypermotility, stereotypies and ataxia induced by ketamine were evaluated using a motor activity cage. To assess the efficacy of BNN27 to reverse non-spatial and spatial recognition memory deficits caused by ketamine, the object recognition task and the object location task were used. Finally, the social interaction test was utilized in order to examine the effects of BNN27 on ketamine-induced social withdrawal. BNN27 (3 and 6 mg/kg, i.p.) attenuated ketamine (10 mg/kg, i.p.)-induced ataxia and to some extent also hypermotility. BNN27 (3–6 mg/kg, i.p.) counteracted ketamine (3 mg/kg, i.p.)-induced non-spatial and spatial recognition memory deficits. Further, BNN27 (6 mg/kg, i.p.) reduced the ketamine (8 mg/kg, i.p.)-induced social isolation. Our findings show that BNN27 is sensitive to glutamate hypofunction produced by ketamine since it reduced schizophrenia-like behavioural deficits induced by this NMDA receptor antagonist in rats. © 2019 Elsevier Lt