It is now well established that acute and chronic alcohol alters the strength of synaptic transmission by modulating ion channels and receptors. A number of evidence suggest that the persistence of these changes, over days or weeks, explains, at least in part, alcohol long-lasting deleterious effects on behavior. Long-term potentiation (LTP) and depression (LTD) are the two most widely studied paradigms of such persistent synaptic alterations. To date, acute and chronic alcohol effects on LTP have been examined in structures of the limbic system (hippocampus, amygdala) and in the cortex. However, no study has been carried out in the nucleus accumbens (NAcc), a region believed to underlie the rewarding properties of all drugs of abuse, including that of alcohol. Furthermore, LTD has been largely ignored by all these studies. This leaves a number of questions regarding the cellular underpinnings of LTD regulation by alcohol. We hypothesize that LTD results from the interactions between synaptic potentials and backpropagating (b-APs), and that b-APs mediate EtOH effects on LTD. We believe that this attempt to bring together various fields of neurosciences (neuronal information processing and synaptic plasticity) will further our understanding of the cellular mechanisms employed by drugs of abuse to sustain their effects over long periods of time. The goal of this project is to examine the role of backpropagating action potentials in mediating the acute effects of alcohol on long- term potentiation depression (LTD), a well-known form of learning and memory paradigms. This study will be carried out in the nucleus accumbens, a major brain region responsible for the rewarding properties of all drugs of abuse. We believe this will represent an important step towards elucidating the cellular mechanisms underlying long-term persistent negative effects of alcohol on behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA016908-01A2
Application #
7531958
Study Section
Special Emphasis Panel (ZAA1-CC (12))
Program Officer
Liu, Qi-Ying
Project Start
2009-09-05
Project End
2011-08-31
Budget Start
2009-09-05
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$231,706
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655