engleski

EFfects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulphate on seizure threshold, locomotor activity, motor coordination and body weight in mice

Introduction: Neurosteroid dehydroepiandrosterone sulphate (DHEAS) has been associated to various functions in the central nervous system, including modulation of neuronal plasticity and survival, memory and behaviour, also showing therapeutic potential in different neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on GABA-A receptors and its facilitatory action on NMDA-receptor mediated glutamatergic neurotransmission, might lead to enhanced neuronal excitability and seizures and thus limit DHEAS therapeutic applications. Materials and methods: To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic neurosteroid treatment on picrotoxin-, pentylentetrazole- and NMDA-induced seizures in mice. DHEAS has been administered intraperitoneally in adult or aged mice of both sexes, either acutely in doses 10, 25 and 50 mg/kg or repeatedly once daily for 4 weeks in a 10 mg/kg dose. The intravenous convulsant infusion was given 30 min following single (acute treatment) or the last (chronic treatment) DHEAS administration and the thresholds for several convulsive signs were determined. The effects of acute and chronic DHEAS treatment on the locomotor activity, motor coordination and body weight of the animals have been also observed. Results: The results failed to demonstrate significant effects of both acute and chronic DHEAS administration, either on the doses of tested convulsants needed to produce convulsive signs, or on the locomotor activity, motor coordination and body weight in adult or aged mice of both sexes. Conclusions: Although our results suggest that DHEAS might be safe for various potential therapeutic applications, additional studies supporting these findings are needed.

acute and chronic treatment; neurosteroid; DHEAS; mice; seizure threshold; locomotor activity; motor coordination; body weight

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