engleski

Effects of chronic DHEAS administration on seizure threshold, locomotor activity, motor coordination and body weight in male and female mice

Dehydroepiandrosterone sulphate (DHEAS) is a neurosteroid associated to various important brain functions, such as neuronal plasticity, cognition and emotions. It appears that the effects of DHEAS in the central nervous system are primarily mediated through its action on several neurotransmitter systems, including GABAergic and glutamatergic neurotransmission, which are also involved in regulating the balance between excitation and inhibition in the brain. It is possible that enhancement of brain excitability and seizures might limit DHEAS potential therapeutic applications. In order to investigate the effects of chronic neurosteroid treatment, DHEAS has been administered intraperitoneally to female and male mice once daily for 4 weeks in a dose of 10 mg/kg. The effects of long-term DHEAS administration on the picrotoxin-, pentylentetrazole- and NMDA-induced seizures, locomotor activity, motor coordination and body weight of the animals of both sexes have been studied. Chronic DHEAS has not modified the locomotor activity, motor coordination and body weight of both male and female mice. The results also failed to demonstrate significant effects of long-term DHEAS treatment on the doses of intravenously administered picrotoxin, pentylentetrazole and NMDA, needed to produce convulsant signs in male and in female mice. However, sex differences in the susceptibility to seizures became more prominent following chronic DHEAS administration to mice. Although our findings suggest that long-term DHEAS treatment might be safe for various potential therapeutic applications, they also support reported interaction of DHEAS with male and female hormonal status, which may underline observed sex differences in the relationship between DHEAS and various health outcomes.

dehydroepiandrosterone sulphate; mice; sex differences; seizure threshold; motor activity; body weight

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