TY - JOUR
T1 - Combined Amperometry and Electrochemical Cytometry Reveal Differential Effects of Cocaine and Methylphenidate on Exocytosis and the Fraction of Chemical Release
AU - Zhu, Wanying
AU - Gu, Chaoyi
AU - Dunevall, Johan
AU - Ren, Lin
AU - Zhou, Xuemin
AU - Ewing, Andrew G.
N1 - Funding Information:
We acknowledge support from the European Research Council (ERC Advanced Grant), the Knut and Alice Wallenberg Foundation in Sweden, the Swedish Research Council (VR), and the U.S. National Institutes of Health (NIH).
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/3/22
Y1 - 2019/3/22
N2 - Amperometry with nanotip electrodes has been applied to show cocaine and methylphenidate not only trigger declines in vesicle content and exocytotic catecholamine release in a model cell line but also differentially change the fraction of transmitter released from each individual vesicle. In addition, cocaine accelerates exocytotic release dynamics while they remain unchanged after methylphenidate treatment. The parameters from pre-spike feet for the two drugs are also in opposition, suggesting this aspect of release is affected differentially. As cocaine and methylphenidate are psychostimulants with similar pharmacologic action but have opposite effects on cognition, these results might provide a missing link between the regulation of exocytosis and vesicles and the effect of this regulation on cognition, learning, and memory. A speculative chemical mechanism of the effect of these drugs on vesicle content and exocytosis is presented.
AB - Amperometry with nanotip electrodes has been applied to show cocaine and methylphenidate not only trigger declines in vesicle content and exocytotic catecholamine release in a model cell line but also differentially change the fraction of transmitter released from each individual vesicle. In addition, cocaine accelerates exocytotic release dynamics while they remain unchanged after methylphenidate treatment. The parameters from pre-spike feet for the two drugs are also in opposition, suggesting this aspect of release is affected differentially. As cocaine and methylphenidate are psychostimulants with similar pharmacologic action but have opposite effects on cognition, these results might provide a missing link between the regulation of exocytosis and vesicles and the effect of this regulation on cognition, learning, and memory. A speculative chemical mechanism of the effect of these drugs on vesicle content and exocytosis is presented.
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U2 - 10.1002/anie.201813717
DO - 10.1002/anie.201813717
M3 - Article
C2 - 30688389
AN - SCOPUS:85061795853
SN - 1433-7851
VL - 58
SP - 4238
EP - 4242
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 13
ER -