Selective alterations of the CB1 receptors and the fatty acid amide hydrolase in the ventral striatum of alcoholics and suicides.
Recent studies in rodents have suggested a role for the central endocannabinoid system in the regulation of mood and alcohol related behaviors. Alcohol use disorder is often associated with suicidal behavior. In the present study, we examined whether abnormalities in the endocannabinoid system in the ventral striatum are associated with alcohol dependence and suicide. The levels of CB1 receptors, receptor-mediated G-protein signaling, and activity and level of the fatty acid amide hydrolase (FAAH) were analyzed postmortem in the ventral striatum of alcohol-dependent nonsuicides (CA, n=9), alcohol-dependent suicides (AS, n=9) and nonpsychiatric controls (C, n=9). All subjects underwent a psychological autopsy, and toxicological and neuropathological examinations. The levels of the CB1 receptors and the CB1 receptor-mediated G-protein signaling were significantly lower in the ventral striatum of CA compared to the control group. However, these parameters were elevated in AS when compared to CA group. The activity of FAAH enzyme was lower in CA compared to the control group while it was found to be significantly higher in AS compared with CA group. These findings suggest that alcohol dependence is associated with the downregulation of the CB1 receptors, while suicide is linked to the upregulation of these receptors in the ventral striatum. Alteration in the activity of FAAH enzyme that regulates the anandamide (AEA) content might in turn explain differences in the CB1 receptor function in alcohol dependence and suicide. These findings may have etiological and therapeutic implications for the treatment of alcohol addiction and suicidal behavior.
Vinod
K Yaragudri
KY
Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. vyaragudri@nki.rfmh.org
Kassir
Suham A
SA
Hungund
Basalingappa L
BL
Cooper
Thomas B
TB
Mann
J John
JJ
Arango
Victoria
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D000581:Amidohydrolases / Q000378:metabolism*; D000704:Analysis of Variance; D001345:Autoradiography / Q000379:methods; D001479:Basal Ganglia / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D011485:Protein Binding / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013405:Suicide; D014316:Tritium / Q000493:pharmacokinetics; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007099:Imipramine; D043884:Receptor, Cannabinoid, CB1; D014316:Tritium; D000099252:Fatty Acid Amide Hydrolases; C024316:cianopramine