LAUSR

Abstract The clinical onset of schizophrenia often coincides with cannabis use in adolescents and young adults. However, the neurobiological consequences of this co‐morbidity are not well understood. In this study, we examined the effects of &Dgr;9‐THC exposure during early adulthood on schizophrenia‐related behaviors using a developmental mouse model of schizophrenia. Phencyclidine (PCP) or saline was administered once in neonatal mice (at P7; 10 mg/kg). In turn, &Dgr;9‐THC or saline was administered sub‐acutely later in life to cohorts of animals who had received either PCP or saline (P55–80, 5 mg/kg). Mice who were administered PCP alone displayed behavioral changes in the Morris water waze (MWM) and pre‐pulse inhibition (PPI) task paradigm that were consistent with schizophrenia‐related phenotypes, but not in the locomotor activity or novel object recognition (NOR) task paradigms. Mice who were administered PCP and then received &Dgr;9‐THC later in life displayed behavioral changes in the locomotor activity paradigm (p < 0.001) that was consistent with a schizophrenia‐related phenotype, as well as potentiated changes in the NOR (p < 0.01) and MWM (p < 0.05) paradigms as compared to mice that received PCP alone. Decreased cortical receptor expression of NMDA receptor 1 subunit (NR1) was observed in mice that received PCP and PCP + &Dgr;9‐THC, while mice that received &Dgr;9‐THC and PCP + &Dgr;9‐THC displayed decreases in CB1 receptor expression. These findings suggest that administration of &Dgr;9‐THC during the early adulthood can potentiate the development of schizophrenia‐related behavioral phenotypes induced by neonatal exposure to PCP in mice. HighlightsNeonatal PCP (P7) administration induces schizophrenia‐like phenotypes.In this model, &Dgr;9‐THC administration in young adults potentiates these phenotypes.&Dgr;9‐THC or combined PCP + &Dgr;9‐THC decreases cortical CB1 receptor expression.PCP or combined PCP + &Dgr;9‐THC decreases cortical NR1 receptor expression.