Περίληψη:
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, hole-board, 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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Συγγραφείς:
Kokras, N.
Dioli, C.
Paravatou, R.
Sotiropoulos, M.G.
Delis, F.
Antoniou, K.
Calogeropoulou, T.
Charalampopoulos, I.
Gravanis, A.
Dalla, C.
Λέξεις-κλειδιά:
(3beta,21 dihydroxy 20 epoxy 5 pregnene); 4 aminobutyric acid; antidepressant agent; anxiolytic agent; estrogen; glutamic acid; glutamine; neuroprotective agent; neurosteroid; progesterone; sex hormone; unclassified drug; BNN27 compound; prasterone, 4 aminobutyric acid brain level; adult; animal experiment; animal model; animal tissue; antidepressant activity; Article; blood sampling; controlled study; depression; drug structure; estrogen blood level; experimental behavioral test; exploratory behavior; female; forced swim test; GABAergic system; glutamatergic synapse; hippocampus; hole board test; light dark cycle; locomotion; male; neuroprotection; nonhuman; open field test; prefrontal cortex; priority journal; progesterone blood level; rat; sex difference; sex hormone determination; tranquilizing activity; animal; chemistry; drug effect; metabolism; pharmacology; physiology; sexual characteristics; Wistar rat, Animals; Dehydroepiandrosterone; Exploratory Behavior; Female; Hippocampus; Locomotion; Male; Neurosteroids; Prefrontal Cortex; Rats; Rats, Wistar; Sex Characteristics
