The proposed project will investigate the neuroadaptive and synaptic changes associated with drug addiction within the cholinergic neuronal network system. Our recent findings examined the role of a specific subpopulation of striatal neurons in the rat, called cholinergic interneurons, in cocaine reinforcement. These cells are activated (in a dose-dependent manner) following the acute self-administration of cocaine in the shell compartment of the nucleus accumbens and in the ventromedial quadrant of the dorsal striatum (two targets of the mesolimbic dopamine pathway). In addition, these cells possess dopamine receptors that enable them to respond to cocaine-induced dopamine changes. These recent findings implicate these cholinergic interneurons as potential key targets of drug addiction.
Two specific aims are proposed: 1) To quantify changes in dopamine D5 (a D1-type receptor) and D2 receptor expression at the light microscopic level following chronic (2 weeks) self-administration of cocaine and following withdrawal (2 weeks) from cocaine. Although this experiment has not been performed specifically in the cholinergic interneurons, previous findings suggests that we should find a global increase in dopamine D1-type receptors following chronic treatment with cocaine (Self and Nestler 1995; Koob, 1996) and a global increase in dopamine D2 receptors following withdrawal in the striatum (Sousa et al., 1999); and 2) To quantify synapses onto cholinergic interneurons and synapses by these neurons onto striatal neurons at the electron microscopic level following chronic self-administration and withdrawal from cocaine. The uniqueness of this proposal lies in the ability of the sponsor's laboratory to look at drug changes at the microcircuit level with respect to a specific cell population in an area of the brain that is key to addiction. This is the only lab to have linked cholinergic interneurons anatomically to addiction using Fos. Moreover, we are investigating these changes with respect to the cholinergic system in an attempt to identify functionally relevant changes in the system that may explain relapse, craving, and other drug-related phenomena. These findings may help to develop a more effective treatment for those that suffer from drug addiction by identifying a specific microcircuit of the brain to target at a particular stage of addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA016807-02
Application #
6806490
Study Section
Special Emphasis Panel (ZRG1-F10 (29))
Program Officer
Babecki, Beth
Project Start
2003-09-29
Project End
2006-09-28
Budget Start
2004-09-29
Budget End
2005-09-28
Support Year
2
Fiscal Year
2004
Total Cost
$27,722
Indirect Cost
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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Bao, Hong; Berlanga, Monica L; Xue, Mingshan et al. (2007) The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila. Mol Cell Neurosci 34:662-78
Berlanga, Monica Lisa; Simpson, Taylor Kathryn; Alcantara, Adriana Angelica (2005) Dopamine D5 receptor localization on cholinergic neurons of the rat forebrain and diencephalon: a potential neuroanatomical substrate involved in mediating dopaminergic influences on acetylcholine release. J Comp Neurol 492:34-49