In contrast to the receptor binding studies, reduced cortical CB 1R mRNA and protein expression have been found in the post-mortem DLPFC (Brodmann's areas 9 and 46) in SCZ ( Eggan et al, 2008 Eggan et al, 2010), whereas another study ( Koethe et al, 2007) found no change in the density of CB 1R immunopositive cells in the anterior cingulate cortex in SCZ. Looking in other cortical regions, we have previously shown an increase in the binding of the selective cannabinoid antagonist SR141716A in the anterior cingulate cortex of patients with SCZ post-mortem ( Zavitsanou et al, 2004), a finding that was confirmed in the posterior cingulate cortex ( Newell et al, 2006). Urigüen et al (2009) reported that immunodensity of CB 1R in the frontal cortex was significantly decreased in antipsychotic-treated patients with SCZ but not in drug-free patients ( Urigüen et al, 2009). Dean et al (2001) found increased binding of the CB 1R agonist CP 55 940, in the dorsolateral prefrontal cortex (DLPFC, Brodmann's area 9) in patients with SCZ that was independent of cannabis use before death and in caudate-putamen that appeared to be related to premorbid cannabis use in these patients. In the cortex, the CB 1R is expressed mainly on presynaptic terminals of GABAergic inhibitory interneurons ( Eggan and Lewis, 2007).Ībnormalities in the CB 1R in cortical regions in schizophrenia (SCZ) have been reported in a number of studies. The CB 1R is considered to mediate the majority of the psychoactive properties of cannabis ( Ameri, 1999) and is expressed abundantly throughout the human brain ( Glass et al, 1997). Our findings confirm the existence of a CB 1R dysregulation in SCZ and underline the need for further investigation of the role of this receptor particularly in those diagnosed with paranoid SCZ.Ĭannabis and cannabis-related drugs act principally through two seven-transmembrane-domain, G protein-coupled receptors termed the cannabinoid 1 (CB 1R) and cannabinoid 2 (CB 2R) receptors that are also activated by endogenous ligands termed endocannabinoids. In contrast, no significant differences were observed in mRNA expression between the different disease subtypes and the control group. When ANCOVA was employed, this effect was strengthened (F(2,67)=6.048, p=0.004) with paranoid SCZ patients differing significantly from the control ( p=0.004) and from the non-paranoid group ( p=0.016). ![]() Post hoc tests indicated that this main effect was due to patients with paranoid SCZ having 22% higher levels of CB 1R binding compared with the control group. There was a main effect of diagnosis on CP 55 940 binding quantified across all layers of the DLPFC (F(2,71)=3.740, p=0.029). ![]() Results were analyzed using one-way analysis of variance (ANOVA) and post hoc Bonferroni tests and with analysis of covariance (ANCOVA) to control for demographic factors that would potentially influence CB 1R expression. All cases were obtained from the University of Sydney Tissue Resource Centre. Receptor density was investigated using autoradiography with the CB 1R ligand CP 55 940 and CB 1R mRNA expression was measured using quantitative RT-PCR in a cohort of 16 patients with paranoid SCZ, 21 patients with non-paranoid SCZ and 37 controls matched for age, post-mortem interval and pH. In the present study, we examined cannabinoid CB 1 receptor (CB 1R) binding and mRNA expression in the dorsolateral prefrontal cortex (DLPFC) (Brodmann's area 46) of SCZ patients and controls, post-mortem. ![]() A number of studies suggest a dysregulation of the endogenous cannabinoid system in schizophrenia (SCZ).
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