Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment.

Details

Serval ID
serval:BIB_876B680C2B0D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Immunodensity and mRNA expression of A2A adenosine, D2 dopamine, and CB1 cannabinoid receptors in postmortem frontal cortex of subjects with schizophrenia: effect of antipsychotic treatment.
Journal
Psychopharmacology
Author(s)
Urigüen L., García-Fuster M.J., Callado L.F., Morentin B., La Harpe R., Casadó V., Lluis C., Franco R., García-Sevilla J.A., Meana J.J.
ISSN
1432-2072 (Electronic)
ISSN-L
0033-3158
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
206
Number
2
Pages
313-324
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
RATIONALE: Dopamine D2 receptors are the main target of antipsychotic drugs. In the brain, D2 receptors coexpress with adenosine A2A and CB1 cannabinoid receptors, leading to functional interactions.
OBJECTIVES: The protein and messenger RNA (mRNA) contents of A2A, D2, and CB1 receptors were quantified in postmortem prefrontal cortex of subjects with schizophrenia.
MATERIALS AND METHODS: The study was performed in subjects suffering schizophrenia (n=31) who mainly died by suicide, matched with non-schizophrenia suicide victims (n=13) and non-suicide controls (n=33). The density of receptor proteins was evaluated by immunodetection techniques, and their relative mRNA expression was quantified by quantitative real-time polymerase chain reaction.
RESULTS: In schizophrenia, the densities of A2A (90+/-6%, n=24) and D2-like receptors (95+/-5%, n=22) did not differ from those in controls (100%). Antipsychotic treatment did not induce changes in the protein expression. In contrast, the immunodensity of CB1 receptors was significantly decreased (71+/-7%, n=11; p<0.05) in antipsychotic-treated subjects with schizophrenia but not in drug-free subjects (104+/-13%, n=11). The relative mRNA amounts encoding for A2A, D2, and CB1 receptors were similar in brains of drug-free, antipsychotic-treated subjects with schizophrenia and controls.
CONCLUSIONS: The findings suggest that antipsychotics induce down-regulation of CB1 receptors in brain. Since A2A, D2, and CB1 receptors coexpress on brain GABAergic neurons and reductions in markers of GABA neurotransmission have been identified in schizophrenia, a lower density of CB1 receptor induced by antipsychotics could represent an adaptative mechanism that reduces the endocannabinoid-mediated suppression of GABA release, contributing to the normalization of cognitive functions in the disorder.
Keywords
Adult, Aged, Analysis of Variance, Antipsychotic Agents/pharmacology, Antipsychotic Agents/therapeutic use, Female, Frontal Lobe/drug effects, Gene Expression Regulation/drug effects, Gene Expression Regulation/genetics, Humans, Male, Middle Aged, Postmortem Changes, RNA, Messenger/metabolism, Receptor, Adenosine A2A/genetics, Receptor, Adenosine A2A/metabolism, Receptor, Cannabinoid, CB1/genetics, Receptor, Cannabinoid, CB1/metabolism, Receptors, Dopamine D2/genetics, Receptors, Dopamine D2/metabolism, Schizophrenia/drug therapy, Schizophrenia/metabolism, Suicide/psychology, Young Adult
Pubmed
Web of science
Create date
10/02/2015 9:18
Last modification date
20/08/2019 14:46
Usage data