Neurosteroid Modulation of Glutamate Release in Hippocampal Neurons: Lack of an Effect of a Chronic Prenatal Ethanol Exposure Paradigm

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Abstract
Background: Pregnenolone sulfate (PREGS) is a promnesic neurosteroid that is abundantly expressed in the hippocampus of rodents. Studies have shown that the modulation of postsynaptic ligand‐gated ion channels by this neurosteroid is impaired in preparations from the brains of fetal ethanol‐exposed animals. In this study, we examined whether the presynaptic actions of PREGS also are affected by exposure to ethanol in utero.Methods: Rat dams were exposed to one of the following diets during pregnancy: (1) 5% ethanol liquid diet, (2) 0% ethanol liquid diet with pair‐feeding, and (3) ad libitum controls. We then studied the presynaptic actions of PREGS on (1) alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor‐mediated miniature excitatory postsynaptic currents (mEPSCs) recorded from cultured hippocampal neurons in the whole‐cell patch‐clamp configuration and (2) paired‐pulse facilitation of NMDA receptor‐dependent excitatory postsynaptic potentials that were intracellularly recorded from CA1 pyramidal neurons in hippocampal slices from adult rats.Results: Chronic prenatal ethanol exposure affected neither basal mEPSC frequency nor its potentiation by PREGS. Basal paired‐pulse facilitation (i.e., in the absence of PREGS) was unaffected by fetal ethanol exposure. Chronic prenatal ethanol exposure did not affect the PREGS‐induced potentiation of paired‐pulse facilitation.Conclusions: Chronic prenatal ethanol exposure does not affect the basal probability of glutamate release in immature or mature hippocampal neurons. Moreover, the presynaptic actions of the neurosteroid PREGS also are unaffected by this exposure. Given that modulation of glutamate release could have a role in the mechanism of the promnesic actions of this neurosteroid, future studies are warranted to determine whether PREGS can ameliorate learning and memory deficits in fetal ethanol‐exposed animals.

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