Cocaine Increases Dopamine Release by Mobilization of A Synapsin-Dependent Reserve Pool
Cocaine Increases Dopamine Release by Mobilization of A Synapsin-Dependent Reserve Pool
Cocaine Increases Dopamine Release by Mobilization of A Synapsin-Dependent Reserve Pool
Brief Communications
Cocaine primarily exerts its behavioral effects by enhancing dopaminergic neurotransmission, amplifying dopamine-encoded sensori-
motor integration. The presumed mechanism for this effect is inhibition of the dopamine transporter, which blocks dopamine uptake and
prolongs the duration of dopamine in the extracellular space. However, there is growing evidence that cocaine can also augment dopa-
mine release. Here, we directly monitored the actions of cocaine on dopamine release by using electrochemical detection to measure
extracellular dopamine in the striatum of anesthetized mice. Cocaine enhanced the levels of striatal dopamine produced by electrical
stimulation of dopaminergic neurons. Even after pretreatment with -methyl-p-tyrosine, which depletes the readily releasable pool of
dopamine, cocaine was still capable of elevating dopamine levels. This suggests that cocaine enhances dopamine release by mobilizing a
reserve pool of dopamine-containing synaptic vesicles. To test this hypothesis, we examined electrically evoked dopamine release in
synapsin I/II/III triple knock-out mice, which have impaired synaptic vesicle reserve pools. Knock-out of synapsins greatly reduced the
ability of cocaine to enhance dopamine release with long stimulus trains or after depletion of the newly synthesized pool. We therefore
conclude that cocaine enhances dopamine release and does so by mobilizing a synapsin-dependent reserve pool of dopamine-containing
synaptic vesicles. This capacity to enhance exocytotic release of dopamine may be important for the psychostimulant actions of cocaine.
Key words: cocaine; synapsin; dopamine; in vivo voltammetry; storage pools; psychostimulant
it is possible that cocaine and other psychostimulants enhance of release and uptake in mouse brain slices in the absence of D(3) recep-
dopamine release by increasing presynaptic Ca 2 influx and tors. Neuroscience 112:39 49.
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the synapsin-mediated effect of cocaine on the dopamine reserve Subsecond dopamine release promotes cocaine seeking. Nature
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