title: Using In Vitro Electrophysiology to Screen Medications: Accumbal Plasticity as an Engram of Alcohol Dependence.
abstract: The nucleus accumbens (NAc) is a central component of the mesocorticolimbic reward system. Increasing evidence strongly implicates long-term synaptic neuroadaptations in glutamatergic excitatory activity of the NAc shell and/or core medium spiny neurons in response to chronic drug and alcohol exposure. Such neuroadaptations likely play a critical role in the development and expression of drug-seeking behaviors. We have observed unique cell-type-specific bidirectional changes in NAc synaptic plasticity (metaplasticity) following acute and chronic intermittent ethanol exposure. Other investigators have also previously observed similar metaplasticity in the NAc following exposure to psychostimulants, opiates, and amazingly, even following an anhedonia-inducing experience. Considering that the proteome of the postsynaptic density likely contains hundreds of biochemicals, proteins and other components and regulators, we believe that there is a large number of potential molecular sites through which accumbal metaplasticity may be involved in chronic alcohol abuse. Many of our companion laboratories are now engaged in identifying and screening medications targeting candidate genes and its products previously linked to maladaptive alcohol phenotypes. We hypothesize that if manipulation of such target genes and their products change NAc plasticity, then that observation constitutes an important validation step for the development of novel therapeutics to treat alcohol dependence.
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: R
authors.initials: R
authors.lastname: Renteria
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Jeanes
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: R A
authors.initials: RA
authors.lastname: Mangieri
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: E Y
authors.initials: EY
authors.lastname: Maier
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: D M
authors.initials: DM
authors.lastname: Kircher
authors.affiliation: University of Texas at Austin, Austin, TX, United States.
authors.forename: T R
authors.initials: TR
authors.lastname: Buske
authors.affiliation: University of Texas at Austin, Austin, TX, United States. Electronic address: ramorris@mail.utexas.edu.
authors.forename: R A
authors.initials: RA
authors.lastname: Morrisett
mesh_terms: D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D002491:Central Nervous System Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects*
chemical_list: D002491:Central Nervous System Agents
keywords: Long-term depression; Medium spiny neuron; Neuroadaptation; Nucleus accumbens; Synaptic