Single cocaine exposure does not alter striatal presynaptic dopamine function in mice: an [18F]-FDOPA PET study
File(s)Accepted Manuscript.pdf (956.59 KB)
Accepted version
Author(s)
Type
Journal Article
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 (KiCer: 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.
Date Issued
2017-09-18
Date Acceptance
2017-09-12
Citation
Journal of Neurochemistry, 2017, 143 (5), pp.551-560
ISSN
1471-4159
Publisher
Wiley
Start Page
551
End Page
560
Journal / Book Title
Journal of Neurochemistry
Volume
143
Issue
5
Copyright Statement
This is the peer reviewed version of the following article: Bonsall, D. R., Kokkinou, M., Veronese, M., Coello, C., Wells, L. A. and Howes, O. D. (), Single cocaine exposure does not alter striatal presynaptic dopamine function in mice: an [18F]-FDOPA PET study. J. Neurochem.. Accepted Author Manuscript. , which has been published in final form at https://dx.doi.org/10.1111/jnc.14223. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Subjects
PET
behaviour
cocaine
dopamine
mouse
1109 Neurosciences
Neurology & Neurosurgery
Publication Status
Published