Browsing by Subject "cocaine"

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Chronic Forced and Free Exercise on Cocaine Place Conditioning and Glutamatergic Synaptic Plasticity in the VTA
(2018) Do, Minh; Morikawa, Hitoshi
Exercise may be useful in preventing substance use disorders and addiction. It is well known that chronic exercise, both forced and voluntary, decreases addiction vulnerability in rodent models and likely in humans. However, the mechanism by which chronic exercise accomplishes this has not been fully evaluated. Here, a conditioned place preference (CPP) paradigm was used to measure the learning of cocaine-associated environmental cues in two groups of rats following a period of both forced and free running. It is shown that rats subjected to chronic forced running displayed no significant deviation in learning of contextual cues paired with cocaine through CPP. On the other hand, rats subjected to chronic free running displayed a notable decrease in acquisition of cocaine-CPP. To investigate the mechanism by which chronic exercise affects cocaine-CPP, we will conduct future electrophysiological studies in the ventral tegmental area (VTA), an area that has been widely implicated in the natural reward circuitry of the brain. The VTA and its role in addiction has been studied extensively by the Morikawa Lab, with one previous study finding that repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine-CPP. Essentially, we expect to observe a decrease in long-term potentiation (LTP) of NMDA-mediated glutamatergic synaptic plasticity in the VTA and consequently, a decrease in cocaine-CPP following both chronic forced and free exercise. If observed, our findings will suggest that decreased plasticity of glutamatergic transmission may be responsible for decreased addiction vulnerability through chronic exercise.
Identification of human biomarkers for cocaine addiction diagnosis
(2008) Romack, Rebecca; Mayfield, R. Dayne
Addiction is a result of long-lasting behavioral changes including tolerance (the need for escalating doses to achieve the same effect) and dependence (physical symptoms manifested during abstinence). It is estimated that 35.3 million Americans have tried cocaine at least once, 6.1 million have used in the past year, and 2.4 million have used it in the past month according to the National Household Survey on Drug Abuse report in 2006, indicating the need for accurate diagnosis of dependence among a large portion of the population. It is important to diagnose cocaine use and dependence by finding definitive markers, termed biomarkers, of such a disease state. For comparison, blood tests for the presence of cocaine are only effective for the 20 minutes to several hours that the drug remains in the body. At present diagnosis of cocaine dependence requires subjective psychological and physical testing and interviews. The goal is to use microarrays to identify a specific set of biomarkers which can reliably determine a diagnosis of cocaine addiction. The impact of this research includes development of novel pharmacotherapies to prevent addiction and relapse and to improve the quality of life and productivity of addicted and recovering individuals and their communities. This experiment uses global gene expression analysis to identify changes in the RNA of cocaine addicts versus non-addicted individuals. Total RNA is extracted from whole blood samples, purified, hemoglobin transcripts are removed, and RNA is quantified with Nanodrop spectroscopy. The RNA is the hybridized to oligonucleotide microarrays containing 49,000 genes. This project will ultimately produce useful data on diagnostic biomarkers of cocaine addiction. It can help clinicians to diagnose addicts and to determine what drugs a patient has been using long term. The project is a collaboration that will identify correlations between gene expression patterns and subject behavior as reported by UTMB Galveston and UTHSC-Houston, Page 3 thus enabling unambiguous diagnosis of addiction. My role in the project is to obtain high quality, ultra pure RNA from whole blood samples, with the goal of discovering biomarkers of cocaine addiction.