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 Since DA is found in high concentration in the retina, we previously examined retinal function in cocaine-withdrawn patients using spectral ganzfeld electroretinography (ERG).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 We replicated this finding in a second group of cocaine-withdrawn patients and controls. The goal of the proposed study is to determine in cocaine-withdrawn patients whether ERG blue cone responses may serve as biologic markers of decreased brain DA. In order to achieve this goal, we will evaluate cone function using ERG in a consecutive series of 50 cocaine-withdrawn patients and determine whether blue cone ERG responses correlate with two known measures of DA function, cerebrospinal fluid (CSF) and urinary levels of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 Cocaine-withdrawn patients will be recruited from among in-patients of the Substance Abuse Treatment Program at the Veterans Administration Medical Center, East Orange, New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study will determine whether such technique can serve as a biologic marker of decreased central DA function in cocaine-withdrawn patients.

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National Institute on Drug Abuse (NIDA)
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Human Development Research Subcommittee (NIDA)
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University of Medicine & Dentistry of NJ
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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
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