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Single cocaine exposure does not alter striatal presynaptic dopamine function in mice: an [(18) F]-FDOPA PET study

Research output: Contribution to journalArticle

D R Bonsall, M Kokkinou, M Veronese, C Coello, L A Wells, O D Howes

Original languageEnglish
JournalJournal of Neurochemistry
Early online date18 Sep 2017
DOIs
Publication statusPublished - Dec 2017

King's Authors

Abstract

Cocaine is a recreational drug of abuse that binds to the dopamine transporter (DAT), preventing reuptake of dopamine into presynaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and postsynaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on presynaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography (PET) have revealed impaired presynaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use μ-PET imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of presynaptic dopamine function. We show that a dose of 20mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p<0.001). However, dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (Ki(Cer) : 0.0097 min(-1) vs. 0.0112 min(-1) in vehicle controls, p>0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p>0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to presynaptic dopaminergic neurons are not initiated following a single exposure to the drug. This article is protected by copyright. All rights reserved.

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