Cocaine and the Vesicular Monoamine Transporter-2

University Of Utah, Salt Lake City UT

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Abstract

DESCRIPTION (provided by applicant): According to the Monitoring the Future and Substance Abuse and Mental Health Services Association studies for 2001, the prevalence of cocaine use is extremely high among adolescents and young adults. However, most studies involving this drug are in the adult population. Preliminary data in our laboratory demonstrate that cocaine causes a greater increase in vesicular dopamine (DA) uptake in PND 90 compared to PND 40 rats. The vesicular monoamine transporter-2 (VMAT-2) is the main transporter protein involved in sequestration of cytoplasmic DA into vesicles for storage and release. The mechanism for the age-dependent differential effect on VMAT-2 is unknown. Several investigators have demonstrated that nerve terminals contain at least two vesicle pools, including a plasma membrane and a cytosolic pools, which undergo different mechanisms of vesicle recycling to regulate sequestration of monoamines. We speculate that differences in trafficking among these pools as a function of age may underlie the cocaine-induced differential effect observed. This proposal tests the hypothesis that the greater effect of cocaine on VMAT-2 function in PND 90 compared to PND 40 rats is due to greater drug-induced trafficking of vesicles from the plasma membrane to a non-membrane-associated (i.e., perhaps cytoplasmic) pool. The results from these studies will provide insight into differences in VMAT-2 function during development, as well as the age-dependent differential effect of psychostimulants on VMAT-2 function. This has implications not only for development of treatment of drugs of abuse, but also provide further understanding of striatal neuron function.