Developmental Differences in the Sensitivity of Spontaneous and Miniature IPSCs to Ethanol

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Abstract
Ethanol (EtOH) consumption by juveniles and adolescents is an important public health problem. Recent studies have indicated that adolescent animals are less sedated by EtOH than adult animals and experience less motor impairment. Thus, human adolescents may be able to consume more EtOH prior to sedation, putting them at greater risk for EtOH addiction and other negative consequences of EtOH use. However, the mechanisms underlying this developmental difference are unknown. One contributing factor may be gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inhibition, which is known to produce sedation. We have shown that evoked, GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) are less powerfully enhanced by EtOH in neurons from juvenile or adolescent animals than in those from adult animals; however, the mechanisms of this developmental difference in sensitivity are unknown.Using whole-cell recording, we tested the response of spontaneous and miniature GABA(A) receptor-mediated IPSCs (sIPSCs and mIPSCs) to EtOH in rat hippocampal slices from animals representing two distinct developmental stages: adolescent and adult.We found significantly greater EtOH-induced enhancement of the frequency of sIPSCs in cells from adult animals compared to those from adolescent animals. Although EtOH also increased the frequency of mIPSCs, this effect was not age dependent. EtOH did not significantly affect the kinetics of mIPSCs.We conclude that the sensitivity of GABA(A) receptor-mediated inhibitory processes to EtOH increases with development from the adolescent period to adulthood, and that this is likely mediated by developmental changes in the effect of EtOH on interneuron excitation.