Because deficits in GAD67 and CB1R mRNA levels are strongly correlated in the PFC in schizophrenia (6), we used genetically-engineered mice to investigate the plausibility of the hypothesis that a deficiency in GAD67 mRNA expression induces a corresponding reduction in CB1R mRNA, versus the alternative hypothesis that lower CB1R mRNA leads to a reduction in GAD67 expression. We found that GAD67+/− mice with a mean 37% decrease in GAD67 mRNA in the mPFC had CB1R mRNA levels that were significantly 16% lower than WT mice, and that GAD67 and CB1R mRNA levels were positively correlated across animals. Together, these data demonstrate that reduced GAD67 mRNA expression in mice is sufficient to produce lower levels of CB1R mRNA in the mPFC. In contrast, GAD67 mRNA levels were not changed in either peripubertal or adult mice with reduced CB1R mRNA expression, demonstrating that reduced CB1R mRNA expression does not affect GAD67 mRNA levels. In concert with our previous finding that alterations in CB1R and GAD67 mRNA expression in schizophrenia are strongly correlated (r=0.64; p=0.001) (6), these data support the hypothesis that reduced
