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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Panepistimiou 3, 415-00, Larissa, Greece

    Nikolaos Pitsikas & Elli Zoupa

  2. Department of Pharmacology, School of Medicine, and Institute of Molecular Biology & Biotechnology, Foundation of Research & Technology-Hellas, University of Crete, Heraklion, Greece

    Achille Gravanis

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  1. Nikolaos Pitsikas
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  2. Elli Zoupa
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  3. Achille Gravanis
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Correspondence to Nikolaos Pitsikas.

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All authors, except Achille Gravanis, declare that they have not any competing financial interests in relation to the work described. Dr. Achille Gravanis is the co-founder of spin-off Bionature EA LTD, proprietary of compound BNN27 (patented with the WO 2008/ 1555 34 A2 number at the World Intellectual Property Organization).

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Pitsikas, N., Zoupa, E. & Gravanis, A. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts cognitive deficits induced by the D1/D2 dopaminergic receptor agonist apomorphine in rats. Psychopharmacology 238, 227–237 (2021). https://doi.org/10.1007/s00213-020-05672-z

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