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- Title
Altered CB1 receptor coupling to G-proteins in the post-mortem caudate nucleus and cerebellum of alcoholic subjects.
- Authors
Erdozain, Amaia M.; Rubio, Marina; Meana, J. Javier; Fernández-Ruiz, Javier; Callado, Luis F.
- Abstract
Biochemical, pharmacological and genetic evidence suggests the involvement of the endocannabinoid system in alcohol dependence. The aim of the present study was to evaluate the state of CB1 receptors in post-mortem caudate nucleus, hippocampus and cerebellum of alcoholic subjects.CB1 protein levels were measured by Western blot, CB1 receptor density and affinity by [(3)H]WIN55,212-2 saturation assays and CB1 functionality by [(35)S]GTPγS binding assays. Experiments were performed in samples from 24 subjects classified as non-suicidal alcoholics (n = 6), suicidal alcoholics (n = 6), non-alcoholic suicide victims (n = 6) and control subjects (n = 6).Alcoholic subjects presented hyperfunctional CB1 receptors in the caudate nucleus resulting in a higher maximal effect in both alcoholic groups compared to the non-alcoholic groups (p < 0.001). Conversely, in the cerebellum the non-suicidal alcoholic subjects showed hypofunctional receptors with lower maximal effect and potency (p < 0.001). No changes were found in the CB1 protein expression in either region. In the hippocampus of alcoholic subjects, no changes were observed either in the functionality, density or protein levels.Our data support an association between endocannabinoid system activity and alcoholism. The modifications reported here could be either a consequence of high lifetime ethanol consumption or a vulnerability factor to develop alcohol addiction.
- Subjects
ALCOHOLISM; CANNABINOID receptors; G proteins; CAUDATE nucleus; HIPPOCAMPUS (Brain); WESTERN immunoblotting; HYDROCARBON metabolism; BASAL ganglia; CELL receptors; CEREBELLUM; HETEROCYCLIC compounds; MEMBRANE proteins; POSTMORTEM changes; RADIOISOTOPES; RADIOISOTOPES in medical diagnosis; SUICIDE; CASE-control method
- Publication
Journal of Psychopharmacology, 2015, Vol 29, Issue 11, p1137
- ISSN
0269-8811
- Publication type
journal article
- DOI
10.1177/0269881115599388