Magnitude and ethanol sensitivity of tonic GABAA receptor-mediated inhibition in dentate gyrus changes from adolescence to adulthood.
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(A)R)-mediated neurotransmission in the hippocampal formation, particularly that which is driven by extrasynaptic GABA(A)Rs, 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(A)Rs 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(A)R-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.
Fleming
Rebekah L
RL
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA. rebekah.fleming@duke.edu
Wilson
Wilkie A
WA
Swartzwelder
H Scott
HS
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*
D001640:Bicuculline; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D000431:Ethanol; D018756:GABA Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A