Chronic administration of dehydroepiandrosterone sulfate (DHEAS) primes for facilitated induction of long-term potentiation via sigma 1 (σ1) receptor: Optical imaging study in rat hippocampal slices

Dehydroepiandrosterone sulfate (DHEAS), one of the most abundant neurosteroids synthesized de novo in the nervous system, has well characterized effects on memory and cognitive performances. However, little is known about the underlying synaptic mechanisms. In this study, we investigated the effects of chronic administration of DHEAS (20 mg/kg for 7 days) on the plasticity of Schaffer collateral-CA1 synapses by applying an optical recording technique on the hippocampal slices stained with voltage-sensitive dyes. We report here that chronically administered DHEAS significantly facilitated the induction of frequency-dependent LTP, termed DHEAS-facilitated LTP. While tetanus of at least 50 pulses (at 100 Hz) were required to induce LTP in control rats, only 20 pulses were needed in DHEAS-treated animals. In contrast DHEA, the non-sulfated form of DHEAS, had no facilitating effect on the induction of LTP. We found that chronically administered DHEAS did not alter the presynaptic glutamate release in response to both single pulse and tetanic stimulation, suggesting that certain alterations happened in postsynaptic neurons. Co-administration of the sigma 1 (σ1) receptor antagonists, haloperidol or NE100, with DHEAS completely inhibited the DHEAS-facilitated LTP. However, acute administration of σ1 receptor antagonists to the slices did not affect the induction of DHEAS-facilitated LTP, suggesting that σ1 receptor is a key target of chronic actions of DHEAS but is not involved in the induction of DHEAS-facilitated LTP. Our findings provide evidence that chronically administered DHEAS plays a priming role in inducing a facilitated synaptic plasticity probably via a chronic activation of σ1 receptor in rat hippocampal CA1 pyramidal cells.