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.

Détails

ID Serval
serval:BIB_876B680C2B0D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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.
Périodique
Psychopharmacology
Auteur(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
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
206
Numéro
2
Pages
313-324
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
10/02/2015 9:18
Dernière modification de la notice
20/08/2019 14:46
Données d'usage