7/8 NADIA UO1 Adolescent Alcohol and Neurocircuitry Mediating Ethanol Reinforcement

Project: Research projectResearch Project--Cooperative Agreements

Description

? DESCRIPTION (provided by applicant): The vast majority of American children begin consuming alcohol prior to high school graduation and episodes of heavy ethanol consumption increase over time (Johnson et al., 1999, 2009). A family history of alcoholism increases the risk that adolescent alcohol consumption is associated with adult alcoholism (Agrawal et al., 2009). Periadolescent ethanol consumption by alcohol-preferring (P) rats increases the reinforcing properties of EtOH in the posterior ventral tegmental area (pVTA) during adulthood (Toalston et al., 2014). NADIA- generated research has indicated that adolescent intermittent ethanol (AIE) exposure results in persistent alterations in neuroimmune factors, choline acetyltransferase (ChAT), increased anxiety, and changes in histone acetylation altering neurocircuitry (Vetreno et al., 2014; Sakharkar et al., 2014). As a new component of the NADIA Consortium, the long-range objectives of this study are to determine the effects of AIE on the motivational, reinforcing
and anxiolytic properties of EtOH during adulthood within the pVTA and central nucleus of the amygdala (CeA). The impact of a genetic predisposition to high alcohol consumption on the effects of AIE will be determined by making assessments in P rats. The overall hypothesis is that AIE results in lasting neurotransmitter system, epigenetic, and structural alterations in regions critical for motivation, reinforcement, and anxiety. The goals of the application are 1) to
assess alterations in the reinforcing properties of EtOH in the pVTA and CeA produced by AIE, 2) to evaluate the neurochemical response to EtOH in the pVTA induced by AIE, 3) to determine if histone deacetylase (HDAC) inhibitor treatment reverses the alterations produced by AIE, 4) to determine the impact of AIE on probabilistic decision-making. In Aim 1, we will test the hypothesis that AIE induced neuroadaptations within the pVTA alter EtOH reinforcement and the neurochemical response to EtOH during adulthood. In Aim 2, we will test the hypothesis that AIE induced neuroadaptations within the pVTA can be reversed by site specific administration of HDAC inhibitor during adulthood. In Aim 3, we will test the hypothesis that AIE induced neuroadaptations within the CeA alter the reinforcing and anxiolytic properties of EtOH during adulthood. In Aim 4, we will test the hypothesis that AIE has altered the probabilistic decision-making (an animal model of impulsivity) during adulthood. This is a highly significant project that
will attempt to elucidate the complex factors that underlie the effects of AIE on adult EtOH usage.
StatusActive
Effective start/end date9/1/158/31/20

Funding

  • National Institutes of Health: $315,900.00

Fingerprint

Ethanol
Alcohols
Ventral Tegmental Area
Histone Deacetylase Inhibitors
Anti-Anxiety Agents
Reinforcement (Psychology)
Alcohol Drinking
Alcoholism
Decision Making
Anxiety
Choline O-Acetyltransferase
Impulsive Behavior
Genetic Predisposition to Disease
Acetylation
Epigenomics
Histones
Neurotransmitter Agents
Motivation
Animal Models

Keywords

  • Medicine(all)