Effects of exposure to THC in adolescent mice genetic model of schizophrenia

The development of schizophrenia depends on interactions between genetic and environmental risk factors. The mutation of the serine racemase enzyme gene, which converts L-serine into D-serine, is suggested as one of the genetic risk factors for schizophrenia. Among environmental risk factors, exposure to cannabis during adolescence is associated with the development of schizophrenia. Studies exposing wild-type (WT) adolescent mice to Δ-9-tetrahydrocannabinol (THC), have reported a reduction in the prepulse inhibition response (PPI) in adulthood. Other studies found no difference. Our objective is to investigate the effects of exposure to THC in adolescence on cognition and behavior in adult mice a genetic model of schizophrenia, with these animals being mutants for SRR. We administered THC or vehicle (VHC), orally, to C57Bl/6J (WT) or SRR-/- mice on postnatal days P30-P50 in increasing doses (2.5; 3.0; 5.0 ; 10 mg/kg). The PPI, open field and spatial recognition tests (SRT) were performed after P120. Using two-way ANOVA and the Tukey post test, we observed that SRR-/- VHC mice have a reduced PPI response of 85dB, in the 120ms interval compared to WT VHC (p<0.05 ). WT THC have a lower PPI than SRR-/- THC in the pre-pulse of 85dB, in the 120ms interval (p<0.05). SRR-/- THC have a higher PPI than SRR-/- VHC in the pre-pulse of 85dB in the 60ms and 120ms intervals (p<0.05). In the open field test, WT and SRR-/- mice treated with THC remained longer in the center when compared to mice treated with VHC of both genotypes (p<0.05). In the SRT, SRR-/- THC had an increased spatial discrimination index compared to SRR-/- VHC (p<0.01). Our data suggest that exposure to THC during adolescence was able to prevent the deficit in PPI and SRT in SRR-/- animals in adulthood, in addition, treatment with THC in adolescence had an anxiolytic effect in mice at that adulthood.