title: Ethanol inhibits excitatory neurotransmission in the nucleus accumbens of adolescent mice through GABAA and GABAB receptors.
abstract: Age-related differences in various acute physiological and behavioral effects of alcohol have been demonstrated in humans and in other species. Adolescents are more sensitive to positive reinforcing properties of alcohol than adults, but the cellular mechanisms that underlie such a difference are not clearly established. We, therefore, assessed age differences in the ability of ethanol to modulate glutamatergic synaptic transmission in the mouse nucleus accumbens (NAc), a brain region importantly involved in reward mechanisms. We measured field excitatory postsynaptic potentials/population spikes (fEPSP/PS) in NAc slices from adolescent (22-30 days old) and adult (5-8 months old) male mice. We found that 50mM ethanol applied in the perfusion solution inhibits glutamatergic neurotransmission in the NAc of adolescent, but not adult, mice. This effect is blocked by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline and by the GABAB receptor antagonist CGP 55845. Furthermore, bicuculline applied alone produces a stronger increase in the fEPSP/PS amplitude in adult mice than in adolescent mice. Activation of GABAA receptors with muscimol produces a stronger and longer lasting depression of neurotransmission in adolescent mice as compared with adult mice. Activation of GABAB receptors with SKF 97541 also depresses neurotransmission more strongly in adolescent than in adult mice. These results demonstrate that an increased GABA receptor function associated with a reduced inhibitory tone underlies the depressant action of ethanol on glutamatergic neurotransmission in the NAc of adolescent mice.
authors.affiliation: The Karolinska Institute, Department of Physiology and Pharmacology, Section of Molecular Neurophysiology, Sweden. karima.chergui@ki.se
authors.forename: Devesh
authors.initials: D
authors.lastname: Mishra
authors.forename: Karima
authors.initials: K
authors.lastname: Chergui
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects*; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects*; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018079:Receptors, GABA; C085075:CGP 55845A; D009118:Muscimol; D000431:Ethanol; D001640:Bicuculline