A 2004 National Survey on Drug Use and Health reported that about 34 million Americans have had some exposure to cocaine at least once in their lifetime. The addictive properties of this drug is well recognized and results in an increased direct cost in medical care as well as indirect cost due to increased societal burden. The Roskamp Institute, located in Sarasota Florida is currently engaged in research into discovery of biological biomarkers and novel treatments for substance abuse. Michael Mullan MD PhD (Director of the Roskamp Institute), during his medical training in London, worked on addiction and determined that certain addictive disorders had a significant genetic component. It is now well-established that substance dependency has a prominent genetic component and approximately 40-60% of the vulnerability to substances can be sufficiently attributed to these genetic factors. Previously, the Roskamp Institute scientists demonstrated that a polymorphism in gene for mu-opioid receptor (OPRM1 +118A) is a risk for alcohol dependency. This Roskamp Institute team then examined the frequency of OPRM1 +118A carrying genotypes and alleles in several groups of substance-dependent cases compared to individuals with no history of reported substance abuse. These Roskamp Institute scientists found that the OPRM1 +118 polymorphism is a genetic risk factor for substance dependence but not specific to a particular substance (findings published in the journal Molecular Psychiatry).
Dr. Fiona Crawford (Associate director, Roskamp Institute) and Dr. Michael Mullan (Director, Roskamp Institute) received an award from the Counterdrug Technology Assessment Center (CTAC) to evaluate the newly emerged genomics and proteomics technologies and determine their usefulness in finding potential biomarkers and treatments for substance abuse. Dr. Fiona Crawford along with her Roskamp Institute team using this genomic technology investigated the fundamental transcriptional responses occurring in neurons as a consequence of acute cocaine exposure over a time period. These Roskamp Institute scientists used GeneChip Operating Software from Affymetrix to compare the genomic response in neuronal cells exposed to cocaine compared to cells that were not exposed and showed a time-dependent increase of genes associated with pro-inflammatory and immune responses. These findings suggest that the inflammatory and immune systems maybe involved in modulating response to an acute cocaine exposure (originally published in the Journal of Neurochemistry).
Next, this Roskamp Institute team determined a role of oxidative stress in cocaine exposure in human progenitor neuronal cells. Although, it is evident that cocaine induces oxidative stress in the central nervous system, little is known whether such increase in oxidative stress is also relevant to cell death in cocaine-exposed models. To gain further insight into the role of cocaine-induced oxidative stress, the Roskamp Institute scientists hypothesized that oxidative stress precedes cell death upon cocaine exposure and demonstrated that oxidative stress was significantly increased in neuronal cells treated with cocaine and this phenomenon preceded cell death. Therefore, these findings have implications for cocaine abuse in circumstances where antioxidant system is compromised, as in the aging brain (original findings in the Journal of Neurochemistry International).
The addictive properties of these psychoactive substances is well recognized and results in enormous burden of direct and indirect costs to the US economy. The Roskamp Institute is dedicated to understanding the factors that predispose individuals to substance abuse as well as discover additional molecular targets for therapeutic intervention.
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