title: Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area.
abstract: Enhanced dopamine (DA) neurotransmission from the ventral tegmental area (VTA) to the ventral striatum is thought to drive drug self-administration and mediate positive reinforcement. We examined neuronal firing rates in slices of mouse midbrain following adolescent binge-like alcohol drinking and find that prior alcohol experience greatly enhanced the sensitivity to excitation by ethanol itself (10-50 mM) in a subset of ventral midbrain DA neurons located in the medial VTA. This enhanced response after drinking was not associated with alterations of firing rate or other measures of intrinsic excitability. In addition, the phenomenon appears to be specific to adolescent drinking, as mice that established a drinking preference only after the onset of adulthood showed no change in alcohol sensitivity. Here we demonstrate not only that drinking during adolescence induces enhanced alcohol sensitivity, but also that this DA neuronal response occurs over a range of alcohol concentrations associated with social drinking in humans.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Avegno
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Salling
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Anders
authors.initials: A
authors.lastname: Borgkvist
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Mrejeru
authors.affiliation: Department of Neurobiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Whitebirch
authors.affiliation: Department of Neurology, The Wheeler Center for the Neurobiology of Addiction, Alcoholism and Addiction Research Group, University of California, San Francisco, CA 94143, United States.
authors.forename: Elyssa B
authors.initials: EB
authors.lastname: Margolis
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, NY 10032, United States. Electronic address: ds43@columbia.edu.
authors.forename: David
authors.initials: D
authors.lastname: Sulzer
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States; Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States. Electronic address: nh2298@columbia.edu.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Harrison
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000428:Alcohol Drinking / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D063425:Binge Drinking / Q000473:pathology / Q000503:physiopathology*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002755:Choice Behavior; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013375:Substance Withdrawal Syndrome / Q000473:pathology / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D014836:Volition
chemical_list: D002492:Central Nervous System Depressants; D049452:Green Fluorescent Proteins; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase
keywords: Adolescence; Dopamine; Electrophysiology; Ethanol self-administration; Ventral tegmental area