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Scientific article
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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

Published inPsychopharmacologia, vol. 206, no. 2, p. 313-324
Publication date2009
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
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: Psychopharmacologia, 2009, vol. 206, n° 2, p. 313–324. doi: 10.1007/s00213-009-1608-2
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Article (Published version)
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Identifiers
ISSN of the journal0033-3158
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