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Central 5-HT4 receptor binding as biomarker of serotonergic tonus in humans : a [ 11C ] SB207145 PET study . Identification of a biomarker that can inform on extracellular serotonin ( 5-HT ) levels in the brains of living humans would enable greater understanding of the way brain circuits are modulated by serotonergic neurotransmission . Substantial evidence from studies in animals and humans indicates an inverse relationship between central 5-HT tonus and 5-HT type 4 receptor ( 5-HT4R ) density , suggesting that 5-HT4R receptor density may be a biomarker marker for 5-HT tonus . Here , we investigated whether a 3-week administration of a selective serotonin reuptake inhibitor , expected to increase brain 5-HT levels , is associated with a decline in brain 5-HT4R binding . A total of 35 healthy men were studied in a placebo-controlled , randomized , double-blind study . Participants were assigned to receive 3 weeks of oral dosing with placebo or fluoxetine , 40 mg per day . Brain 5-HT4R binding was quantified at baseline and at follow-up with [ ( 11 ) C ] SB207145 positron emission tomography ( PET ) . Three weeks of intervention with fluoxetine was associated with a 5.2 % reduction in brain 5-HT4R binding ( P=0.017 ) , whereas placebo intervention did not change 5-HT4R binding ( P=0.52 ) . Our findings are consistent with a model , wherein the 5-HT4R density adjusts to changes in the extracellular 5-HT tonus . Our data demonstrate for the first time in humans that the imaging of central 5-HT4R binding may be used as an in vivo biomarker of the central 5-HT tonus .
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Intervention_Control
placebo-controlled
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Intervention_Control
oral dosing with placebo
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Intervention_Pharmacological
fluoxetine , 40 mg per day
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Intervention_Physical
( 11 ) C ] SB207145 positron emission tomography ( PET )
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Outcome_Physical
Brain 5-HT4R binding
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Outcome_Other
positron emission tomography
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Outcome_Physical
brain 5-HT4R binding
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Outcome_Physical
5-HT4R density
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Participant_Condition
humans :
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Participant_Condition
living humans