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

Urigüen, Leyre; García-Fuster, M Julia; Callado, Luis F.; Morentin, Benito; La Harpe, Romano; Casadó, Vicent; Lluis, Carmen; Franco, Rafael; García-Sevilla, Jesús A.; Meana, J Javier

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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
Authors		Urigüen, Leyre García-Fuster, M Julia Callado, Luis F. Morentin, Benito La Harpe, Romano Casadó, Vicent Lluis, Carmen Franco, Rafael García-Sevilla, Jesús A. Meana, J Javier show all authors [1 - 10]
Published in		Psychopharmacology. 2009, vol. 206, no. 2, p. 313-24
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/therapeutic use — Female — Frontal Lobe/drug effects — Gene Expression Regulation/drug effects/genetics — Humans — Male — Middle Aged — Postmortem Changes — RNA, Messenger/metabolism — Receptor, Adenosine A2A/genetics/metabolism — Receptor, Cannabinoid, CB1/genetics/metabolism — Receptors, Dopamine D2/genetics/metabolism — Schizophrenia/drug therapy/metabolism/pathology — Suicide/psychology — Young Adult
Identifiers		DOI: 10.1007/s00213-009-1608-2 PMID: 19652957
Full text		Article (Published version) (271 Kb) - Limited access to UNIGE Other version: http://www.springerlink.com/content/f163738p71125530/fulltext.html
Structures		Faculté de médecine / Section de médecine clinique / Département de santé et de médecine communautaires / Institut de médecine légale
Research group		Neurorécepteurs et ARN (672)
Citation (ISO format)		URIGÜEN, Leyre et al. 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. In: Psychopharmacology, 2009, vol. 206, n° 2, p. 313-24. https://archive-ouverte.unige.ch/unige:5538