Co-occurring substance abuse disorders (SUDs) and mental illness is a major problem in contemporary mental health. Despite advances in understanding the neuropathophysiology of various forms of mental illness or addictions as ideal, non-overlapping entities, the interaction between these disease processes is poorly understood. This Mentored Clinical Scientist Development Award (K08) seeks support for the career development of a psychiatrist/researcher as a translational neuroscientist focused on understanding the neural mechanisms commonly involved in addictions and psychiatric disorders. This award will further a research program characterizing combined animal models of psychiatric illness and addictions while supporting training needed to apply relevant neurobiological assays to dual diagnosis animal models. This research hypothesizes that neural systems abnormalities that cause psychiatric syndromes also cause increased vulnerability to the neurobehavioral process of addiction, and ultimately, a greater frequency of SUDs in the mentally ill. Building on previous work demonstrating an accelerated addiction pattern to cocaine in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia, this research will explore the neurobiological correlates of a sensitizing regimen of daily cocaine injections, the NVHL, and their combination, vs. sham-saline controls to uncover neural systems interactions between these addiction and psychiatric disease models.
Specific Aim 1 will utilize immunohistochemistry to examine patterns of cocaine-induced immediate-early gene (c-Fos) expression to identify group differences in neuronal activation in forebrain circuits commonly implicated in addictions and mental illness.
Specific Aim 2 will utilize microdialysis to examine group differences in cocaine-induced dopamine and serotonin efflux in the NAc.
Specific Aim 3 will utilize microarray technology to examine group differences in patterns of gene expression in the Nucleus Accumbens (NAc), Caudate Putamen (CaPu) and medial Prefrontal Codex (mPfC).

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DA019850-04
Application #
7410083
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Volman, Susan
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$182,566
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
Chambers, R Andrew (2013) Adult hippocampal neurogenesis in the pathogenesis of addiction and dual diagnosis disorders. Drug Alcohol Depend 130:1-12
Chambers, R A; McClintick, J N; Sentir, A M et al. (2013) Cortical-striatal gene expression in neonatal hippocampal lesion (NVHL)-amplified cocaine sensitization. Genes Brain Behav 12:564-75
Vohs, Jenifer L; Chambers, R Andrew; O'Donnell, Brian F et al. (2012) Auditory steady state responses in a schizophrenia rat model probed by excitatory/inhibitory receptor manipulation. Int J Psychophysiol 86:136-42
Berg, S A; Czachowski, C L; Chambers, R Andrew (2011) Alcohol seeking and consumption in the NVHL neurodevelopmental rat model of schizophrenia. Behav Brain Res 218:346-9
Vohs, Jenifer L; Chambers, R Andrew; Krishnan, Giri P et al. (2010) GABAergic modulation of the 40 Hz auditory steady-state response in a rat model of schizophrenia. Int J Neuropsychopharmacol 13:487-97
Chambers, Robert Andrew; Sentir, Alena M; Engleman, Eric A (2010) Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions. Psychopharmacology (Berl) 212:73-83
Chambers, R Andrew; Sentir, Alena M; Conroy, Susan K et al. (2010) Cortical-striatal integration of cocaine history and prefrontal dysfunction in animal modeling of dual diagnosis. Biol Psychiatry 67:788-92
Chambers, R Andrew; Connor, Michael C; Boggs, Cathy J et al. (2010) The Dual Diagnosis Physician-infrastructure Assessment Tool: examining physician attributes and dual diagnosis capacity. Psychiatr Serv 61:184-8
Chambers, R Andrews (2010) Dazed and confused by self-medication. Am J Psychiatry 167:600; author reply 600-1
Kalapatapu, Raj K; Chambers, R (2009) Novel Objective Biomarkers of Alcohol Use: Potential Diagnostic and Treatment Management Tools in Dual Diagnosis Care. J Dual Diagn 5:57-82

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