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 [18F]altanserin. [18F]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 
[18F]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 [18F]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 [18F]altanserin are discussed.