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Temporal characterisation of amphetamine‐induced dopamine release assessed with [ 11 C]raclopride in anaesthetised rodents
Author(s) -
Houston Gavin C.,
Hume Susan P.,
Hirani Ella,
Goggi Julian L.,
Grasby Paul M.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10296
Subject(s) - raclopride , amphetamine , dopamine , chemistry , microdialysis , pharmacology , neurotransmitter , medicine , neuroscience , dopamine receptor d2 , receptor , biology , biochemistry
Competition between endogenous neurotransmitters and radiolabelled tracers, as measured by positron emission tomography (PET), may provide a measure of endogenous neurotransmitter flux in vivo. For example, carbon‐11 labelled raclopride has been effectively used to monitor dopamine release following pharmacological and behavioural manipulations. The current study describes a rodent model of amphetamine‐induced [ 11 C]raclopride reduction, which allowed the characterisation of the dose–response and temporal dynamics of this reduction over a 24‐h time course. Over the range studied, a monotonic dose–response relationship between amphetamine dose and [ 11 C]raclopride reduction was observed. When compared with previously published microdialysis data, an approximate 16% reduction in [ 11 C]raclopride binding potential was associated with a ∼25‐fold increase in extracellular dopamine. A reduction of 20–30% in raclopride binding was observed 30 min after amphetamine injection (4 mg/kg IP). This reduction in [ 11 C]raclopride binding persisted for 4 h but returned to baseline by 8 h. The data suggest a persistent amphetamine‐induced raclopride displacement in rodents and reinforce findings from nonhuman primates that a simple competitive occupancy model may not adequately explain the temporal characteristics of the amphetamine‐induced decrease in radiotracer binding. Synapse 51:206–212, 2004. © 2003 Wiley‐Liss, Inc.