Patients with schizophrenia exhibit alterations in neuroanatomy, particularly an enlargement of the lateral ventricles, but it remains unclear if these structural changes cause the behavioral deficits associated with the disease or if they are simply secondary to an initial biochemical insult (Shenton ME et al., 2001, Schizophrenia Research, 49, 32-33). We have developed a line of transgenic mice overexpressing a wildtype isoform of the G-protein subunit Gαs (Gαswt) that exhibits a number of cognitive deficits associated with schizophrenia (see Kelly MP et al., 2005, SFN abstract). Here we explore if these cognitive deficits are due to neuroanatomical abnormalities such as those observed in schizophrenia patients. In sagittal sections (Lateral 0.84-1.32mm), Gαswt transgenic mice exhibit enlarged lateral ventricles, reduced caudate putamen, and reduced nucleus accumbens with no change in total brain size. Although acute suppression of the transgene during adulthood by doxycycline rescues the observed cognit...