Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims.
BACKGROUND
Alcoholism is often comorbid with mood disorders and suicide. We recently reported an upregulation of CB(1) receptor-mediated signaling in the dorsolateral prefrontal cortex (DLPFC) of subjects with major depression who died by suicide. In the present study, we sought to determine whether the changes in depressed suicides would also be present in alcoholic suicides and whether the endocannabinoid (EC) system plays a role in suicide in alcoholism.


METHODS
The density of CB(1) receptor and its mediated [(35)S]GTP gamma S signaling were measured in the DLPFC of alcoholic suicides (AS) (n = 11) and chronic alcoholics (CA) (n = 11). The levels of ECs were measured by a liquid chromatograph/mass spectrometry.


RESULTS
The CB(1) receptor density was higher in AS compared with the CA group in the DLPFC. Western blot analysis confirmed a greater immunoreactivity of the CB(1) receptor in AS. The CB(1) receptor-mediated [(35)S]GTP gamma S binding indicated a greater signaling in AS. Higher levels of N-arachidonyl ethanolamide and 2-arachidonylglycerol were observed in the DLPFC of AS.


CONCLUSIONS
The elevated levels of ECs, CB(1) receptors, and CB(1) receptor-mediated [(35)S]GTP gamma S binding strongly suggest a hyperactivity of endocannabinoidergic signaling in AS. EC system may be a novel therapeutic target for the treatment of suicidal behavior.
Vinod
K Yaragudri
KY
Department of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
Arango
Victoria
V
Xie
Shan
S
Kassir
Suham A
SA
Mann
J John
JJ
Cooper
Thomas B
TB
Hungund
Basalingappa L
BL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000378:metabolism*; D001667:Binding, Competitive / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D063388:Endocannabinoids; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013405:Suicide; D013460:Sulfur Isotopes / Q000494:pharmacology; D014316:Tritium / Q000494:pharmacology
D063385:Cannabinoid Receptor Modulators; D003511:Cyclohexanols; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D013460:Sulfur Isotopes; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol