An epidemic of cocaine abuse has occurred in the United States. An alternative therapeutic approach for treating cocaine abuse, based on interrupting the distribution of cocaine to the dopamine neuronal uptake sites, is being developed. In this proposal an injectable microcapsule formulation containing a catalytic antibody to cocaine will be developed and evaluated for release characteristics in rodent in vivo experiments. More specifically, the usefulness of incorporating the catalytic antibody, Mab 15A10, within biodegradable microcapsules will be assessed by determining the area under the plasma concentration-time curve, plasma half-lives, and the volume of distribution after injections of different concentrations of Mab 15A10 in rodents. In addition, the effectiveness of Mab 15A10 released from biodegradable microcapsules will be assessed by measuring the formulation's ability to shift dose-response curves produced by acute and chronic daily injections of cocaine. Basically, the ability of various doses of acute and chronic daily injections of cocaine to alter locomotor activity, brain concentrations of dopamine and cocaine, and dopamine D2 and D1 receptor levels will be determined in the presence and absence of biodegradable microcapsules containing Mab 15A10.Dopamine D2 and D1 receptor will be measured in rodent basal ganglia, amygdala, and brain tissue anterior and medial to the caudate putamen using in vitro receptor binding assays.
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