期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 24, 期 9, 页码 1037-1045出版社
SAGE PUBLICATIONS INC
DOI: 10.1097/01.WCB.0000126233.08565.E7
关键词
[F-18]altanserin-5HT(2A); receptors-PET; pindolol; citalopram; steady state
The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [F-18]altanserin. [F-18]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [F-18]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A-mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT-induced adverse effect, cortical [F-18]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [F-18]altanserin are discussed.
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