LABORATORY MODELS OF COCAINE SELF ADMINISTRATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: AIM 1. To genotype non-treatment seeking cocaine-dependent volunteers at the DBH locus. Plasma DBH activity will also be measured. AIM 2. To determine the effects of treatment with disulfiram on cocaine self-administration using two human laboratory models of cocaine self-administration. HYPOTHESIS 1: We anticipate that about two-thirds of the population will have the C/C DBH genotype, which is associated with higher DBH activity, and about one-third of the population will have the C/T or T/T genotypes, which are associated with moderate (C/T) or low (T/T) DBH activity. These estimates are based on studies of non-drug using populations, and the distribution of DBH genotypes may be skewed in cocaine-using populations. This study may provide further data in this regard. Measurement of plasma DBH activity will also allow analysis based on actual enzyme activity. HYPOTHESIS 2: We anticipate that disulfiram treatment will be associated with reduced cocaine self-administration. Results of the proposed research will provide information about the predictive value of two different laboratory models of cocaine self-administration. If results from either or both of these laboratory models are congruent with outcomes from published clinical trials of disulfiram, then further research aimed at optimizing design parameters would be indicated to further develop these approaches. The development of valid laboratory models would greatly facilitate the search for more effective treatments for cocaine dependence.