title: Deleterious effects of a low amount of ethanol on LTP-like plasticity in human cortex.
abstract: Ingesting ethanol (EtOH) at low doses during social drinking is a common human behavior for its facilitating effects on social interactions. However, low-dose EtOH may have also detrimental effects that so far are underexplored. Here we sought to test the effects of low-dose EtOH on long-term potentiation (LTP)-like plasticity in human motor cortex. Previous cellular experiments showed that low-dose EtOH potentiates extrasynaptic GABAAR and reduces NMDAR-mediated currents, processes that would limit the expression of LTP. Paired associative transcranial magnetic stimulation (PASLTP) was employed in nine healthy subjects for induction of LTP-like plasticity, indexed by a long-term increase in motor-evoked potential input-output curves. Synaptic α1-GABAAR function was measured by saccadic peak velocity (SPV). Very low doses of EtOH (resulting in blood concentrations of <5 mM) suppressed LTP-like plasticity but did not affect SPV when compared with a placebo condition. In contrast, 1 mg of alprazolam, a classical benzodiazepine, or 10 mg of zolpidem, a non-benzodiazepine hypnotic, decreased SPV but did not significantly affect LTP-like plasticity when compared with placebo. This double dissociation of low-dose EtOH vs alprazolam/zolpidem effects is best explained by the putatively high affinity of EtOH but not alprazolam/zolpidem to extrasynaptic GABAARs and to NMDARs. Findings suggest that enhancement of extrasynaptic GABAAR-mediated tonic inhibition and/or reduction of NMDAR-mediated neurotransmission by EtOH blocks LTP-like plasticity in human cortex at very low doses that are easily reached during social drinking. Therefore, low-dose EtOH may jeopardize LTP-dependent processes, such as learning and memory formation.
authors.affiliation: Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lücke
authors.affiliation: Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Tonio
authors.initials: T
authors.lastname: Heidegger
authors.affiliation: Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Röhner
authors.affiliation: Department of Forensic Toxicology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Toennes
authors.affiliation: Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Krivanekova
authors.affiliation: 1] Department of Neurology, Goethe-University, Frankfurt am Main, Germany [2] Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Müller-Dahlhaus
authors.affiliation: 1] Department of Neurology, Goethe-University, Frankfurt am Main, Germany [2] Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000097:blood / Q000494:pharmacology; D001569:Benzodiazepines / Q000097:blood / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation; D004576:Electromyography; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D011725:Pyridines / Q000097:blood / Q000494:pharmacology; D050781:Transcranial Magnetic Stimulation; D000077334:Zolpidem
chemical_list: D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D001569:Benzodiazepines; D000431:Ethanol; D000077334:Zolpidem; D000525:Alprazolam