The gene for 5-HT1B serotonin receptors has been linked to alcoholism in humans but there is scant evidence for how these receptors modulate ethanol's reinforcing effects. Since 5-HT1B receptors are expressed in different groups of neurons throughout the brain, they must be studied using techniques that have anatomical and pharmacological specificity. For example, it is hypothesized that the 5-HT1B recaptors in the axon terminals of medium spiny neurons that project from nucleus accumbens shell (NAcc) to ventral tegmental area modulate drug reward by inhibiting GABA release, thereby disinhibiting dopaminergic activity. To investigate this idea, it is necessary to examine.just these 5-HT1B receptors and not those in other neurons that regulate other aspects of behavior. Toward!this aim, we will use targeted manipulation of 5-HT-iBexpression in these NAcc neurons. We will examine this hypothesis by measuring changes in ethanol consumption after manipulating the level of 5-HT1B expression in the NAcc.
In Specific Aim 1, we plan to increase 5-HT1B expression using virally-mediated gene transfer and measure the effect on the initiation and maintenance of alcohol drinking behavior.
In Specific Aim 2, we will knockdown expression of 5-HT1B receptors in NAcc shell using RNA interference (RNAi) and measure these same behaviors. Thus, we will use novel molecular techniques to manipulate 5-HT1B expression in a discrete group of neurons and measure the resulting changes in free choice ethanol consumption to evaluate how this receptor regulates reward mechanisms in the brain. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA015981-02
Application #
7282691
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Neuhold, Lisa
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$181,456
Indirect Cost
Name
University of Washington
Department
Psychiatry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195