Ex vivo evaluation of the serotonin 1A receptor partial agonist [³H]CUMI-101 in awake rats.
[³H]CUMI-101 is a 5-HT(1A) partial agonist, which has been evaluated for use as a positron emission tracer in baboon and humans. We sought to evaluate the properties of [³H]CUMI-101 ex vivo in awake rats and determine if [³H]CUMI-101 can measure changes in synaptic levels of serotonin after different challenge paradigms. [³H]CUMI-101 shows good uptake and good specific binding ratio (SBR) in frontal cortex 5.18 and in hippocampus 3.18. Binding was inhibited in a one-binding-site fashion by WAY100635 and unlabeled CUMI-101. The ex vivo B(max) of [³H]CUMI-101 in frontal cortex (98.7 fmol/mg) and hippocampus (131 fmol/kg) agree with the ex vivo B(max) of [³H]MPPF in frontal cortex (147.1 fmol/mg) and hippocampus (72.1 fmol/mg) and with in vitro values reported with 8-OH-DPAT. Challenges with citalopram, a selective serotonin reuptake inhibitor, fenfluramine, a serotonin releaser, and 4-chloro-DL-phenylalanine, a serotonin synthesis inhibitor, did not show any effect on the standardized uptake values (SUVs) in any region. Citalopram did alter SBR, but this was due to changes in cerebellar SUVs. Our results indicate that [³H]CUMI-101 is a good radioligand for imaging 5-HT(1A) high-density regions in rats; however, the results from pharmacological challenges remain inconclusive.
Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York, USA. mikael.palner@gmail.com
Mikael
M
Palner
Mark D
MD
Underwood
Dileep J S
DJ
Kumar
Victoria
V
Arango
Gitte M
GM
Knudsen
J
J
John Mann
Ramin V
RV
Parsey
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D003243:Consciousness; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists / Q000493:pharmacokinetics*; D014316:Tritium / Q000493:pharmacokinetics
D019275:Radiopharmaceuticals; D058825:Serotonin 5-HT1 Receptor Agonists; D014316:Tritium