Psychoactive properties of BNN27, a novel neurosteroid derivate, in male and female rats
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ORIGINAL INVESTIGATION
Psychoactive properties of BNN27, a novel neurosteroid derivate, in male and female rats Nikolaos Kokras 1,2 & Chrysoula Dioli 1 & Rafaella Paravatou 1 & Marinos G. Sotiropoulos 1,3 & Foteini Delis 4 & Katerina Antoniou 4 & Theodora Calogeropoulou 5 & Ioannis Charalampopoulos 6,7 & Achille Gravanis 6,7 & Christina Dalla 1 Received: 7 February 2020 / Accepted: 30 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Νeurosteroids, like dehydroepiandrosterone (DHEA), play an important role in neurodegeneration and neural protection, but they are metabolized in androgens, estrogens, or other active metabolites. A newly developed synthetic DHEA analog, BNN27 ((20R)-3β,21-dihydroxy-17R,20-epoxy-5-pregnene), exerts neurotrophic and neuroprotective actions without estrogenic or androgenic effects. Objectives This study aimed to investigate potential anxiolytic or antidepressant properties of BNN27. Methods Male and female adult Wistar rats were treated with BNN27 (10, 30, or 90 mg/kg, i.p.) and subjected to behavioral tests measuring locomotion, exploration, and “depressive-like” behavior (open field, light/dark box, holeboard, and forced swim tests). The hippocampus and prefrontal cortex were collected for glutamate and GABA measurements, and trunk blood was collected for gonadal hormone analysis. Results Acute high-dose BNN27 reduced locomotion and exploratory behavior in both sexes. Intermediate acute doses (30 mg/kg) of BNN27 reduced exploration and testosterone levels only in males, and enhanced progesterone levels in both sexes. Notably, with the present design, BNN27 had neither anxiolytic nor antidepressant effects and did not affect estrogen levels. Interestingly, acute administration of a low BNN27 dose (10 mg/kg) increased glutamate turnover, GABA, and glutamine levels in the hippocampus. The same dose also enhanced glutamate levels in the prefrontal cortex of males only. Sex differences were apparent in the basal levels of behavioral, hormonal, and neurochemical parameters, as expected. Conclusions BNN27 affects locomotion, progesterone, and testosterone levels, as well as the glutamatergic and GABAergic systems of the hippocampus and prefrontal cortex in a sex-dependent way. Keywords GABA . Steroids . Neuroactive steroids . Sex differences . Glutamate . Behavior . Hippocampus
* Christina Dalla [email protected] 1
2
3
Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece First Department of Psychiatry, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece Present address: Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Hale ΒΤΜ 9002AA, 60 Fenwood Road, Boston, MA 02115, USA
4
Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
5
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Const
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