he long-term objective of this competing continuation is the identification of neurobiological mechanisms in the mesolimbic dopamine (DA) system underlying prolonged voluntary alcohol intake that may lead to harmful alcohol consumption. We observed that chronic alcohol consumption by selectively-bred P rats increased the number of spontaneously active DA neurons in the posterior ventral tegmental area (VTA) and increased basal extracellular DA concentrations in the nucleus accumbens. Furthermore, the alterations in accumbal DA levels persisted during ethanol deprivation. We hypothesize that the observed electrophysiological and neurochemical changes resulted from an increased sensitivity of VTA DA neurons. The proposed experiments are designed to demonstrate increased sensitivity and elucidate possible mechanisms. Extracellular recording techniques and microiontophoresis will be used in unanesthetized paralyzed P rats to examine changes in the sensitivities of receptors on VTA DA neurons. No-net-flex microdialysis experiments will be used to examine basal levels of specific neurotransmitters in the posterior VTA of freely moving P rats to determine if changes in VTA DA neurons result from alterations in afferent neurotransmission. In addition, both electrophysiological and traditional microdialysis methods will be used to examine the heightened responsiveness of VTA DA neurons to subsequent alcohol administration. The results of these studies will provide an understanding of the neuroadaptations produced by chronic alcohol drinking and deprivation and may contribute to the development of pharmacological interventions for the treatment of alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012832-06
Application #
7487004
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Twombly, Dennis
Project Start
2000-04-01
Project End
2011-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
6
Fiscal Year
2008
Total Cost
$263,918
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202