Binding of a tritiated inverse agonist to cannabinoid CB1 receptors is increased in patients with schizophrenia.
This study sought to determine whether cannabinoid-1 (CB(1)) receptor binding was altered in the postmortem dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia (schizophrenia; n=47) compared to controls (n=43). The CB(1) receptor inverse agonist radioligand [(3)H]MePPEP was used to measure specific binding to CB(1) receptors. The specific binding of [(3)H]MePPEP to CB(1) receptors was 20% higher in patients with schizophrenia than in controls. Power analyses suggested that 53 subjects per group would be needed to detect a similar difference in vivo with positron emission tomography (PET) and the structurally related inverse agonist radioligand [(18)F]FMPEP-d(2) (80% statistical power, p<0.05).
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1003, USA.
Kimberly J
KJ
Jenko
Jussi
J
Hirvonen
Ioline D
ID
Henter
Kacey B
KB
Anderson
Sami S
SS
Zoghbi
Thomas M
TM
Hyde
Amy
A
Deep-Soboslay
Robert B
RB
Innis
Joel E
JE
Kleinman
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011760:Pyrrolidinones / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D012044:Regression Analysis; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D014018:Tissue Distribution / Q000187:drug effects; D014316:Tritium / Q000493:pharmacokinetics
C554672:5-((3-fluoromethoxy)phenyl)-3-(1-phenylethylamino)-1-(4-trifluoromethylphenyl)pyrrolidin-2-one; C526255:5-(3-methoxyphenyl)-3-(1-phenylethylamino)-1-(4-trifluoromethylphenyl)pyrrolidin-2-one; C571130:CNR1 protein, human; D005462:Fluorine Radioisotopes; D011760:Pyrrolidinones; D043884:Receptor, Cannabinoid, CB1; D014316:Tritium