Serotonin concentration enhancers at clinically relevant doses reduce [11C]AZ10419369 binding to the 5-HT1B receptors in the nonhuman primate brain
Kai‐Chun Yang, Akihiro Takano, Christer Halldin, Lars Farde, Sjoerd J. Finnema
Translational Psychiatry July 16, 2018 DOI: 10.1038/s41398-018-0178-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical PET imaging study in non-human primates Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Cynomolgus monkeys |
| Interventions | Amphetamine MDMA 5-HTP |
| Dose | amphetamine 1 mg/kg, MDMA 1 mg/kg, 5-HTP 5 mg/kg |
| Measures | Binding potential (BPND) |
| Topics | Serotonin |
| Citations | 17 |
| Key points | Binding of the PET radioligand [11C]AZ10419369 decreased significantly in several brain regions after amphetamine (19-31%), MDMA (16-25%), or 5-HTP (13-31%), indicating the ligand is sensitive to drug-induced changes in serotonin concentration. The authors propose this PET paradigm may be suitable for future human studies of serotonin release. |
Abstract
Abstract 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. [11C]AZ10419369 binds to 5-HT1Breceptors 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 [11C]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 (BPND) values were determined with the equilibrium method (integral interval: 63–123 min) using cerebellum as the reference region.BPNDvalues 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 [11C]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, [11C]AZ10419369 binding is sensitive to changes in 5-HT concentration induced by amphetamine, MDMA or 5-HTP. The robust changes inBPND, 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.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 6
- Safety pharmacology of acute MDMA administration in healthy subjects Journal of Psychopharmacology February 21, 2017
- Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats British Journal of Pharmacology May 26, 2011
- Effect of Some Psychoactive Drugs Used as ‘Legal Highs’ on Brain Neurotransmitters Neurotoxicity Research April 1, 2016
- Subanesthetic doses of ketamine transiently decrease serotonin transporter activity: a PET study in conscious monkeys. Neuropsychopharmacology December 2013
- Metabolism and disposition of 3,4-methylenedioxymethamphetamine ("ecstasy") in baboons after oral administration: comparison with humans reveals marked differences. Journal of Pharmacology and Experimental Therapeutics July 2011
and 1 more in the library