Although cocaine addiction is a devastating social and medical problem in this country, little is known about the physiological actions of cocaine on the thalamo-cortical limbic circuit. This circuit engages cognitive and emotive processing and is thought to be involved in the behavioral dysfunctions observed in addicts. In this proposal, we outline a plan to study the plastic changes produced in the limbic thalamo-cortical circuit as a consequence of repeated administration of cocaine and the modulatory role of dopamine in this circuit. Our overlying hypothesis is that repeated cocaine administration produces enduring changes in the intrinsic electrophysiological properties of the thalamo-cortical circuit, as well as alterations in responses evoked by stimulating dopamine neurons in the VTA. Using intracellular recordings in vivo, we will test this hypothesis by: 1) Study the reciprocal excitatory interconnection between PFC and MD and it modulation by ascending DA afferents in control animals, 2) Study the normative electrophysiological properties of pyramidal cells in the PFC, as well as the effects of VTA and MD stimulation in rats pretreated with repeated cocaine injections, and 3) Establish the nonnative electrophysiological properties of cells in the MD, as well as the effects of VTA and PFC stimulation in animals pretreated with repeated cocaine injections. The results of these experiments will allow us to understand the mechanisms underlying changes in the limbic circuit as a consequence of repeated cocaine administration and will provide a physiological framework for the cognitive and affective deficits that occur as a consequence of cocaine addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA014698-02
Application #
6624231
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (02))
Program Officer
Volman, Susan
Project Start
2002-05-01
Project End
2007-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2003
Total Cost
$219,000
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
Parsegian, Aram; Glen Jr, W Bailey; Lavin, Antonieta et al. (2011) Methamphetamine self-administration produces attentional set-shifting deficits and alters prefrontal cortical neurophysiology in rats. Biol Psychiatry 69:253-9
Kroener, Sven; Lavin, Antonieta (2010) Altered dopamine modulation of inhibition in the prefrontal cortex of cocaine-sensitized rats. Neuropsychopharmacology 35:2292-304
Nogueira, Lourdes; Lavin, Antonieta (2010) Strong somatic stimulation differentially regulates the firing properties of prefrontal cortex neurons. Brain Res 1351:57-63
Trantham-Davidson, Heather; Lavin, Antonieta (2004) Acute cocaine administration depresses cortical activity. Neuropsychopharmacology 29:2046-51
Lavin, Antonieta (2003) Glutamate/monoamine interactions in the limbic thalamus. Ann N Y Acad Sci 1003:422-5