PMID- 30013068
OWN - NLM
STAT- MEDLINE
DCOM- 20190204
LR  - 20230926
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Jul 16
TI  - Serotonin concentration enhancers at clinically relevant doses reduce 
      [(11)C]AZ10419369 binding to the 5-HT(1B) receptors in the nonhuman primate 
      brain.
PG  - 132
LID - 10.1038/s41398-018-0178-7 [doi]
LID - 132
AB  - The serotonin (5-HT) system plays an important role in the pathophysiology and 
      treatment of several major psychiatric disorders. Currently, no suitable positron 
      emission tomography (PET) imaging paradigm is available to assess 5-HT release in 
      the living human brain. [(11)C]AZ10419369 binds to 5-HT(1B) receptors and is one 
      of the most 5-HT-sensitive radioligands available. This study applied 5-HT 
      concentration enhancers which can be safely studied in humans, and examined their 
      effect on [(11)C]AZ10419369 binding at clinically relevant doses, including 
      amphetamine (1 mg/kg), 3,4-methylenedioxymethamphetamine (MDMA; 1 mg/kg) or 
      5-hydroxy-L-tryptophan (5-HTP; 5 mg/kg). Twenty-six PET measurements (14 for 
      amphetamine, 6 for MDMA and 6 for 5-HTP) using a bolus and constant infusion 
      protocol were performed in four cynomolgus monkeys before or after drug 
      administration. Binding potential (BP(ND)) values were determined with the 
      equilibrium method (integral interval: 63-123 min) using cerebellum as the 
      reference region. BP(ND) values were significantly decreased in several examined 
      brain regions after administration of amphetamine (range: 19-31%), MDMA (16-25%) 
      or 5-HTP (13-31%). Reductions in [(11)C]AZ10419369 binding were greater in 
      striatum than cortical regions after administration of 5-HTP, while no prominent 
      regional differences were found for amphetamine and MDMA. In conclusion, 
      [(11)C]AZ10419369 binding is sensitive to changes in 5-HT concentration induced 
      by amphetamine, MDMA or 5-HTP. The robust changes in BP(ND), following 
      pretreatment drugs administered at clinically relevant doses, indicate that the 
      applied PET imaging paradigms hold promise to be successfully used in future 
      human studies.
FAU - Yang, Kai-Chun
AU  - Yang KC
AUID- ORCID: 0000-0001-8198-2509
AD  - Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska 
      Institutet, Karolinska University Hospital, Stockholm, Sweden. 
      kai-chun.yang@ki.se.
FAU - Takano, Akihiro
AU  - Takano A
AD  - Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska 
      Institutet, Karolinska University Hospital, Stockholm, Sweden.
FAU - Halldin, Christer
AU  - Halldin C
AD  - Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska 
      Institutet, Karolinska University Hospital, Stockholm, Sweden.
FAU - Farde, Lars
AU  - Farde L
AD  - Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska 
      Institutet, Karolinska University Hospital, Stockholm, Sweden.
AD  - Personalized Health Care and Biomarkers, AstraZeneca PET Science Center at 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Finnema, Sjoerd J
AU  - Finnema SJ
AD  - Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska 
      Institutet, Karolinska University Hospital, Stockholm, Sweden.
AD  - Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180716
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Receptor, Serotonin, 5-HT1B)
RN  - C1LJO185Q9 (5-Hydroxytryptophan)
RN  - CK833KGX7E (Amphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 5-Hydroxytryptophan/*pharmacology
MH  - Amphetamine/pharmacology
MH  - Animals
MH  - Brain/diagnostic imaging/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Macaca fascicularis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Positron-Emission Tomography
MH  - Radiopharmaceuticals/*pharmacokinetics
MH  - Receptor, Serotonin, 5-HT1B/*metabolism
PMC - PMC6048172
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/07/18 06:00
MHDA- 2019/02/05 06:00
PMCR- 2018/07/16
CRDT- 2018/07/18 06:00
PHST- 2017/09/26 00:00 [received]
PHST- 2018/04/03 00:00 [accepted]
PHST- 2018/02/14 00:00 [revised]
PHST- 2018/07/18 06:00 [entrez]
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/02/05 06:00 [medline]
PHST- 2018/07/16 00:00 [pmc-release]
AID - 10.1038/s41398-018-0178-7 [pii]
AID - 178 [pii]
AID - 10.1038/s41398-018-0178-7 [doi]
PST - epublish
SO  - Transl Psychiatry. 2018 Jul 16;8(1):132. doi: 10.1038/s41398-018-0178-7.