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Magnitude and Ethanol Sensitivity of Tonic GABA_A Receptor-Mediated Inhibition in Dentate Gyrus Changes From Adolescence to Adulthood

¹Departments of Psychiatry and ²Pharmacology, Duke University Medical Center; and ³Neurobiology Research Laboratory, Veterans Affairs Medical Center, Durham, North Carolina

Submitted 30 January 2007; accepted in final form 18 March 2007

Ethanol consumption by adolescents is a public health problem of striking importance. Educational and clinical efforts to address this problem have been aided by recent neurobehavioral studies indicating that ethanol disrupts memory and memory-related brain functions more powerfully in adolescent animals than in adults. Still, the mechanisms underlying this developmental sensitivity remain unclear. GABA_A receptor (GABA_AR)-mediated neurotransmission in the hippocampal formation, particularly that which is driven by extrasynaptic GABA_ARs, is enhanced by pharmacologically relevant concentrations of ethanol, and may be, in part, responsible for the modulation of memory and memory-related circuit plasticity. Using hippocampal slices from adolescent and adult rats, we have shown that tonic current mediated by extrasynaptic GABA_ARs is larger in dentate gyrus granule cells from adult animals than in those from adolescents and that 30 mM ethanol enhances inhibitory tonic current more in cells from adolescent rats than in those from adults. It is possible that more powerful promotion of tonic GABA_AR-mediated inhibition by ethanol in the dentate gyrus of adolescent rats, compared with adults, contributes to the developmental differences that have previously been observed with respect to ethanol-induced memory impairment and reduction of synaptic plasticity.

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