Cannabinoid self-administration attenuates PCP-induced schizophrenia-like symptoms in adult rats

Although considerable attention has been paid to the relationship between Cannabis use and schizophrenia, there is a significant uncertainty regarding the role of Cannabis consumption in the pathoetiology of the disorder. We investigated the correlation between voluntary cannabinoid consumption and behavioral traits in an animal model of schizophrenia. Male rats were trained to intravenously self-administer the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN; 12.5 µg/kg/infusion) or vehicle; they subsequently received acute or chronic–intermittent intraperitoneal administration of the non-competitive N-methyl-d-aspartate receptor antagonist phencyclidine (PCP; 2.5 mg/kg) or saline. We report that WIN self-administration attenuates PCP-induced deficits in (i) prepulse inhibition (PPI) of the acoustic startle reflex, (ii) cognitive skills, and (iii) sociability, suggesting that cannabinoid consumption can ameliorate the schizophrenia-like behavioral alterations caused by PCP. A parallel study performed in animals receiving WIN on a non-voluntary basis (experimenter-given) confirmed an ameliorating effect of cannabinoid administration on the symptoms of schizophrenia induced by PCP.