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). Whether cocaine may also potentiate DA release under physiological conditions remains unclear. To investigated cocaine’s effect on DA release in striatum in vivo, C57 and DAT-CI mice (male, ～25 g) anaesthetized with urethane (0.15 g/100 g, i.p.) were used. The use and care of animals was approved and directed by the Institutional Animal Care and Use Committee of Peking University. We found 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 (MFB) in mouse striatum in vivo. Surprisingly, cocaine selectively enhanced the DA release and replenishment from the FRP. Using a cocaine-insensitive-DAT (DAT-CI) mouse model, we found that cocaine-facilitated FRP release is mediated by DAT. In contrast, PRP release is selectively sensitive to D2 receptor (D2R). Finally, FRP and PRP have distinct impacts on locomotor behaviours. Our findings indicate that in addition to blocking DA reuptake, cocaine increases DA release by selectively activating DAT, increasing FRP size, and accelerating FRP replenishment in mouse striatum in vivo.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB135
Poster Communications: Cocaine preferentially potentiates fast releasable vesicle pool in mouse dopaminergic striatum in vivo
P. Zuo1, L. Zhou1, X. Kang1, H. Xu1, B. Zhang1, H. Dou1, F. Zhu1, L. Liu1, S. Guo1, C. Wang1, Q. Li1, S. Wang1, W. Yao1, H. Gu2, Z. Zhou1
1. Peking University, Beijing, China. 2. Ohio State University, Columbus, District of Columbia, United States.
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