Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia

Recent advances in the neurobiology of cannabinoids have renewed interest in the association between cannabis and schizophrenia. Our studies showed that chronic-intermittent phencyclidine (PCP) treatment of rats, an animal model of schizophrenia-like cognitive deficit, impaired recognition memory in the novel object recognition (NOR) test and induced alterations in CB1 receptor functionality and in endocannabinoid levels mainly in the prefrontal cortex. In this region, we observed a significant reduction in GTP41%) accompanied by an increase in the levels of the endocannabinoid 2-AG (+38%) in PCP-treated rats, suggesting that a maladaptation of the endocannabinoid system might contribute to the glutamatergic-related cognitive symptoms encountered in schizophrenia disorders. Moreover, we evaluated the ability of the main psychoactive ingredient of marijuana, 73%) or PCP (-64%), whereas it reversed the PCP-induced increase in 2-AG levels. These results point to the involvement of the endocannabinoid system in this pharmacological model of cognitive dysfunction, with a potentially different role of AEA and 2-AG in schizophrenia-like behaviours and suggest that prolonged cannabis use might aggravate cognitive performances induced by chronic PCP by throwing off-balance the endocannabinoid system.