کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2154465 1090236 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo
چکیده انگلیسی

IntroductionIn vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [11C](+)-PHNO ([11C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [3H]raclopride, which binds to both affinity states.MethodsWe tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(−)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [11C](+)-PHNO and [3H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for 11C and 3H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)−%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure.ResultsIn response to D2 antagonists, partial agonist or full agonist, [11C](+)-PHNO and [3H]raclopride SBRs responded indistinguishably in terms of both ED50 and Hill slope (e.g., (−)-NPA ED50 values are 0.027 and 0.023 mg/kg for [11C](+)-PHNO and [3H]raclopride, respectively). In response to AMPH challenge, [11C](+)-PHNO and [3H]raclopride SBRs were inhibited to the same degree.ConclusionsWe have shown that the SBRs of [11C](+)-PHNO- and [3H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nuclear Medicine and Biology - Volume 35, Issue 1, January 2008, Pages 11–17
نویسندگان
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