Cocaine Preferentially Potentiates Fast Releasable Vesicle Pool in Mouse Dopaminergic Striatum In Vivo

Abstract

Cocaine, an addictive drug, increases extracellular dopamine (DA) concentration in basal ganglion. This effect has been commonly assumed mainly through the inhibition of the uptake activity of DA transporters (DAT), although other mechanisms such as cocaine potentiation of DA release is less examined under physiological conditions. Here we report that two kinetically distinct DA releasable vesicle pools, a fast releasable pool (FRP) and a prolonged releasable pool (PRP), existed following physiological field stimulations at medial forebrain bundle in mouse striatum in vivo. Surprisingly, cocaine selectively enhanced the DA release and replenishment from the FRP. using a cocaine-insensitive-DAT mouse model, cocaine-facilitated FRP (not PRP) release is mediated by DAT. In contrast, PRP (not FRP) release is selectively sensitive to D2 receptor (D2R). Thus, in addition to blocking DA reuptake, cocaine increases DA release through selectively activating DAT, increasing FRP size, and accelerating FRP replenishment in mouse striatum in vivo.