Dose-response study of dehydroepiandrosterone sulfate on dentate gyrus long-term potentiation

Neurosteroids are produced peripherally by endocrine glands, as well as enzymatically in the glia from steroid hormone substrates. GABA receptor sites and Ca2+ channel currents are prime targets for neurosteroid actions, and their effects are concentration dependent. For this reason, and the fact that treatment with one of them, sulfated dehydroepiandrosterone (DHEAS), improves performance in tasks involving memory in aged rats, we explored the effect of this hormone on dentate gyrus long term potentiation (LTP) in a dose-response mode. Intact anesthetized rats (urethane, 1.5 g/kg) were used. Electrodes were stereotaxically positioned in the perforant path and dentate gyrus for stimulation (bifocal) and recording (monofocal). DHEAS (10, 20, and 30 mg/kg, dissolved in Nutralipid 10%) was injected into the femoral vein. Ten animals were used to study the effects of each dose, one injection per animal. Twenty control animals were randomly interspersed within the experimental groups and were injected solely with Nutralipid. The results showed a significant increase in LTP at all doses in relation to baseline values. Further, there were significant increments in amplitude at 20 and 30 mg in relation to 10 mg. However, the data did not reveal significant differences between the 20- and the 30-mg-treated rats. Results are discussed in terms of effects of DHEAS on neurotransmitter and Ca2+ channel ion systems.