title: Temporal characterisation of amphetamine-induced dopamine release assessed with [11C]raclopride in anaesthetised rodents.
abstract: 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 [11C]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 [11C]raclopride reduction was observed. When compared with previously published microdialysis data, an approximate 16% reduction in [11C]raclopride binding potential was associated with a approximately 25-fold increase in extracellular dopamine. A reduction of 20-30% in raclopride binding was observed 30 min after amphetamine injection (4 mg/kg i.p.). This reduction in [11C]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.
authors.affiliation: MRC Cyclotron Unit, Hammersmith Hospital, London W12 ONN, UK.
authors.forename: Gavin C
authors.initials: GC
authors.lastname: Houston
authors.forename: Susan P
authors.initials: SP
authors.lastname: Hume
authors.forename: Ella
authors.initials: E
authors.lastname: Hirani
authors.forename: Julian L
authors.initials: JL
authors.lastname: Goggi
authors.forename: Paul M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D023421:Models, Animal; D020891:Raclopride / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine