Fig. 3.

Schizophrenia Resilience Phenotypes of GLS1 hets. (A) GLS1 hets have reduced rCBV in the HIPP but not in the FC or THAL; WT > GLS1 hets (A1). Within the HIPP subregions, rCBV was significantly reduced in CA1 and SUB (A2). WT > GLS1 hets, *P < .05, numbers per group are given in parentheses. (B) GLS1 het mice show an attenuated response to amphetamine (Amph). Ambulatory distance was measured prior to and after intraperitoneal injection of amphetamine (2 mg/kg) or saline (injection, arrow). WT mice showed a robust increase in activity following Amph, while GLS1 hets, as well as saline-treated mice of both genotypes, showed no increase in activity. WT-Amph > GLS1 het-Amph, GLS1 het-saline, WT-saline, *P < .05. GLS1 hets do respond to higher-dose Amph. (C) While microdialysis measurements showed no genotypic difference in baseline DA recovery, the DA surge following Amph was attenuated in the GLS1 hets. WT-Amph > GLS1-Amph, *P < .05. (D) GLS1 hets displayed clozapine (Cloz)-like potentiation of LI. Low freezing levels were observed in WT and GLS1 het mice under saline- or Cloz-treated conditions prior to testing. Freezing ratios during the tone test showed LI. LIis seen as a lower suppression ratio in pre-exposed (PE) compared with not pre-exposed (NPE) subjects. We observed LI in Cloz-treated WT mice and in saline-and Cloz-treated GLS1 hets but not in saline-treated WT mice. NPE > PE, *P < .05, **P < .01. Cloz-treated GLS1 hets did not show enhanced LI. Thus, GLS1 het mice appear similar to WT mice treated with Cloz. GLS1 het, GLS1 heterozygous mice; HIPP, hippocampus; FC, frontal cortex; THAL, thalamus; WT, wild-type mice; CA1 and CA3, hippocampal subregion; SUB, subiculum; DG, dentate gyrus; EC, entorhinal cortex; RCBV, regional CBV; LI, latent inhibition. Source: Redrawn from Gaisler-Salomon et al³⁸ with permission of the authors.