Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/44119
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Type: Journal article
Title: CB1-independent inhibition of dopamine transporter activity by cannabinoids in mouse dorsal striatum
Author: Price, D.
Owens, W.
Gould, G.
Frazer, A.
Roberts, J.
Daws, L.
Giuffrida, A.
Citation: Journal of Neurochemistry, 2007; 101(2):389-396
Publisher: Blackwell Publishing Ltd
Issue Date: 2007
ISSN: 0022-3042
1471-4159
Statement of
Responsibility: 
Price, David A., Owens, William A., Gould, Georgianna G., Frazer, Alan, Roberts, James L., Daws, Lynette C., Giuffrida, Andrea
Abstract: Cannabinoid drugs are known to affect dopaminergic neurotransmission in the basal ganglia circuitry. In this study, we used in vitro and in vivo techniques to investigate whether cannabinoid agonists and antagonist could affect dopaminergic transmission in the striatum by acting at the dopamine transporter. Incubation of striatal synaptosomes with the cannabinoid agonists WIN55,212-2 or methanandamide decreased dopamine uptake (IC50 = 2.0 μmol/L and 3.1 μmol/L, respectively). A similar inhibitory effect was observed after application of the inactive WIN55,212-2 isomer, S(−)WIN55,212-3. The CB1 antagonist AM251 did not reverse WIN55,212-2 effect but rather mimicked it. WIN55,212-2 and AM251 partially displaced the binding of the cocaine analog [3H]WIN35,428, thus acting as dopamine transporter pseudo-substrates in the high micromolar range. High-speed chronoamperometry measurements showed that WIN55,212-2 (4 mg/kg, i.p.) caused significant release of endogenous dopamine via activation of CB1 receptors, followed by a reduction of dopamine clearance. This reduction was CB1-independent, as it was mimicked by S(−)WIN55,212-3. Administration of AM251 (1 and 4 mg/kg, i.p.) increased the signal amplitude and reduced the clearance of dopamine pressure ejected into the striatum. These results indicate that both cannabinoid agonists and antagonists inhibit dopamine transporter activity via molecular targets other than CB1 receptors.
Keywords: anandamide
basal ganglia
cannabinoid
chronoamperometry
dopamine transporter
striatum
Description: The original publication may be found at www.blackwell-synergy.com
DOI: 10.1111/j.1471-4159.2006.04383.x
Published version: http://dx.doi.org/10.1111/j.1471-4159.2006.04383.x
Appears in Collections:Aurora harvest
Pharmacology publications

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