The rewarding effects of cocaine abuse are due primarily to its effects on the neurotransmission of brain dopamine (DA). Preclinical and clinical studies have shown that cocaine withdrawal is associated with decreased central DA. Since DA is found in high concentration in the retina, we previously examined retinal function in cocaine-withdrawn patients using spectral ganzfeld electroretinography (ERG). We found that patients had significantly reduced blue cone ERG responses compared with matched normal controls. We replicated this finding in a second group of cocaine-withdrawn patients and controls. The goal of the proposed study is to determine in cocaine-withdrawn patients whether ERG blue cone responses may serve as biologic markers of decreased brain DA. In order to achieve this goal, we will evaluate cone function using ERG in a consecutive series of 50 cocaine-withdrawn patients and determine whether blue cone ERG responses correlate with two known measures of DA function, cerebrospinal fluid (CSF) and urinary levels of homovanillic acid (HVA), the major DA metabolite. Cocaine-withdrawn patients will be recruited from among in-patients of the Substance Abuse Treatment Program at the Veterans Administration Medical Center, East Orange, New Jersey. A complete psychiatric evaluation, including psychiatric diagnosis, and cocaine and substance abuse history, will be performed. Random drug-urine screens will be obtained. Patients will receive a low-monoamine diet. An ophthalmological evaluation, including ocular examination and computerized spectral ganzfeld ERG will be performed. Three complete 24-hour urine samples will be collected and a lumbar puncture performed for measurement of HVA levels in urine and CSF, respectively. We will then correlate blue cone ERG responses, first with CSF and then, with urinary HVA levels. ERG is a reliable, noninvasive, easily accessible, repeatable, and inexpensive technique; this study will determine whether such technique can serve as a biologic marker of decreased central DA function in cocaine-withdrawn patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA010336-01A1
Application #
2013561
Study Section
Human Development Research Subcommittee (NIDA)
Project Start
1997-05-20
Project End
1999-04-30
Budget Start
1997-05-20
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Psychiatry
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Enoch, Mary-Anne; Hodgkinson, Colin A; Shen, Pei-Hong et al. (2016) GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations. Alcohol Clin Exp Res 40:93-101
Gorodetsky, E; Bevilacqua, L; Carli, V et al. (2014) The interactive effect of MAOA-LPR genotype and childhood physical neglect on aggressive behaviors in Italian male prisoners. Genes Brain Behav 13:543-9
Enoch, Mary-Anne; Hodgkinson, Colin A; Gorodetsky, Elena et al. (2013) Independent effects of 5' and 3' functional variants in the serotonin transporter gene on suicidal behavior in the context of childhood trauma. J Psychiatr Res 47:900-7
Bevilacqua, Laura; Carli, Vladimir; Sarchiapone, Marco et al. (2012) Interaction between FKBP5 and childhood trauma and risk of aggressive behavior. Arch Gen Psychiatry 69:62-70
Roy, Alec; Hodgkinson, Colin A; Deluca, Vincenzo et al. (2012) Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. J Psychiatr Res 46:72-9
Enoch, M-A; Gorodetsky, E; Hodgkinson, C et al. (2011) Functional genetic variants that increase synaptic serotonin and 5-HT3 receptor sensitivity predict alcohol and drug dependence. Mol Psychiatry 16:1139-46
Liu, Jixia; Zhou, Zhifeng; Hodgkinson, Colin A et al. (2011) Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations. Alcohol Clin Exp Res 35:304-16
Roy, Alec; Gorodetsky, Elena; Yuan, Qiaoping et al. (2010) Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology 35:1674-83
Enoch, Mary-Anne; Hodgkinson, Colin A; Yuan, Qiaoping et al. (2010) The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence. Biol Psychiatry 67:20-7
Roy, A (2004) Relationship of childhood trauma to age of first suicide attempt and number of attempts in substance dependent patients. Acta Psychiatr Scand 109:121-5

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