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Measuring endogenous changes in serotonergic neurotransmission with [11C]Cimbi-36 positron emission tomography in humans.
da Cunha-Bang, Sofi; Ettrup, Anders; Mc Mahon, Brenda; Skibsted, Anine Persson; Schain, Martin; Lehel, Szabolcs; Dyssegaard, Agnete; Jørgensen, Louise Møller; Møller, Kirsten; Gillings, Nic; Svarer, Claus; Knudsen, Gitte M.
Afiliación
  • da Cunha-Bang S; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Ettrup A; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Mc Mahon B; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Skibsted AP; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Schain M; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Lehel S; PET and Cyclotron Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Dyssegaard A; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Jørgensen LM; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Møller K; Department of Neuroanaesthesiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Gillings N; PET and Cyclotron Unit, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Svarer C; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark.
  • Knudsen GM; Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, 2100, Denmark. gmk@nru.dk.
Transl Psychiatry ; 9(1): 134, 2019 04 11.
Article en En | MEDLINE | ID: mdl-30975977
ABSTRACT
Developing positron emission tomography (PET) radioligands for the detection of endogenous serotonin release will enable the investigation of serotonergic deficits in many neuropsychiatric disorders. The present study investigates how acute challenges that aim to increase or decrease cerebral serotonin levels affect binding of the serotonin 2A receptor (5-HT2AR) agonist radioligand [11C]Cimbi-36. In a randomized, double-blind, placebo-controlled, three-arm design, 23 healthy volunteers were PET scanned twice with [11C]Cimbi-36 at baseline and following double-blind assignment to one of three interventions (1) infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram preceded by oral dosing of the 5-HT1AR antagonist pindolol, (n = 8) (2) acute tryptophan depletion (ATD) (n = 7) and (3) placebo (n = 8). Two-sample t-tests revealed no significant group differences in percent change of neocortical [11C]Cimbi-36 binding from baseline to intervention between placebo and citalopram/pindolol (p = 0.4) or between placebo and ATD (p = 0.5). Notably, there was a significantly larger within-group variation in 5-HT2AR binding after intervention with citalopram/pindolol, as compared with placebo (p = 0.007). These findings suggest that neither ATD nor a combination of citalopram and pindolol elicit acute unidirectional changes in serotonin levels sufficient to be detected with [11C]Cimbi-36 PET in neocortex. We suggest that the large interindividual variation in 5-HT2AR binding after citalopram/pindolol reflects that after an acute SSRI intervention, individuals respond substantially different in terms of their brain serotonin levels. Our observation has a potential impact for the understanding of patient responses to SSRI.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transmisión Sináptica / Tomografía de Emisión de Positrones / Neuronas Serotoninérgicas Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male Idioma: En Revista: Transl Psychiatry Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transmisión Sináptica / Tomografía de Emisión de Positrones / Neuronas Serotoninérgicas Tipo de estudio: Clinical_trials Límite: Adult / Female / Humans / Male Idioma: En Revista: Transl Psychiatry Año: 2019 Tipo del documento: Article País de afiliación: Dinamarca