Action Potential Code And Cocaine Modulates Dopamine Release In Mice Striatum in vivo

Abstract

Dopamine is a neurotransmitter crucial for movement, mood, drug addiction and many neural degeneration diseases including Parkinson's disease. Micro electrochemical carbon fiber microelectrode (CFE) can record dopamine release from brain in vivo. Stimulation action potentials (APs) induced secretion of dopamine in mouse brain striatum in vivo. The stimulus pattern is defined as AP code [N, m, f, d] (N = total stimulating number, m = burst-number, f = frequency, d = inter-burst interval) (Duan et al, JNS, 2003). In wide type mice (WT), with fixed AP number N, the evoked dopamine release was strongly modulated by code parameters m, f and d. In contrast to N and f, which regulate dopamine release by [Ca2+]i accumulation, m and/or d may modulate secretion by recycling vesicle pool. To test this hypothesis, we used a knockin mice (KI) with the dopamine transporter (DAT) insensitive to cocaine (Chen et al, PNAS, 2006). In KI vs. WT mice, both amplitude and kinetics of dopamine release was drastically changed following given stimulation AP code. The effect of AP burst number ([144, m, 80Hz, 0.5s],m = 1 vs. 16), or “m-effect”, on dopamine release is increased by > 400% in KI vs. WT mice. As expected, cocaine increased AP-induced dopamine release for blocking DAT in WT but not KI mice. Surprisingly, the presynaptic vesicle recycling is also altered by cocaine in WT vs. KI mice, as revealed by reduced “m-effect” in KI mice. We propose that cocaine affects not only DAT, but also presynaptic dopamine vesicle pool in striatum in mice.Supported by grant from China NSFC and “973” program 0