The specific aims of the proposed experiments are: 1) To determine how NAC1 over expression in the nucleus accumbens (NAc) of rats affects the acquisition, maintenance, and reinstatement of cocaine self- administration. 2) To determine how self-administration of cocaine affects NAc protein levels and localization of the 20S proteasome, the E3 ligase Cul3, and poly-ubiquitinated proteins as well as the activity of the proteasome. 3) To determine how the loss of the NAC1 gene in knockout mice affects cocaine self- administration, the protein levels and localization of the above proteins, and proteasome activity. Experiments will use self-administration as the model of addiction and rats will receive AAV-NAC1 infusions to investigate over expression. The NAc from rats and mice will be dissected and sub fractionated to retrieve the cytosolic, nuclear, and postsynaptic density fractions. Some fractions will then undergo proteasome activity assays. Other fractions will undergo immunoblotting to determine fraction levels of the 20S subunit, Cul3, and poly-ubiquitinated proteins. Together, these findings will provide important new information regarding the neuroplastic changes induced by cocaine addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA021460-03
Application #
7596438
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2007-03-02
Project End
2009-05-31
Budget Start
2009-03-02
Budget End
2009-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$14,772
Indirect Cost
Name
Medical University of South Carolina
Department
Neurosciences
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Berglind, William J; Whitfield Jr, Timothy W; LaLumiere, Ryan T et al. (2009) A single intra-PFC infusion of BDNF prevents cocaine-induced alterations in extracellular glutamate within the nucleus accumbens. J Neurosci 29:3715-9
Peters, Jamie; LaLumiere, Ryan T; Kalivas, Peter W (2008) Infralimbic prefrontal cortex is responsible for inhibiting cocaine seeking in extinguished rats. J Neurosci 28:6046-53
LaLumiere, Ryan T; Kalivas, Peter W (2008) Glutamate release in the nucleus accumbens core is necessary for heroin seeking. J Neurosci 28:3170-7