Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 GTPgammaS binding (-41%) 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, Delta9-tetrahydrocannabinol (THC), to modulate the cognitive dysfunctions and neuroadaptations in the endocannabinoid system induced by PCP. Chronic THC co-treatment worsened PCP-induced cognitive impairment, without inducing any effect per se, and in parallel, it provoked a severe reduction in the levels of the other endocannabinoid, AEA, vs. either vehicle (-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.
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PMID:Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia. 1878 79

The 'cannabinoid hypothesis' of schizophrenia tulates that over-activity of the endocannabinoid system might contribute to the aetiology of schizophrenia. In keeping with this hypothesis, increased expression of CB1 receptors, elevation of the endocannabinoid anandamide (AEA) and cannabinoid-induced cognitive changes have been reported in animal models of schizophrenia and psychotic patients. In this study we measured brain endocannabinoid levels and [35S]GTPgammaS binding stimulated by the CB receptor agonist CP55,940 in rats undergoing withdrawal from subchronic administration of phencyclidine (PCP), a well-established pharmacological model of schizophrenia. We also investigated whether systemic application of the fatty-acid amide hydrolase (FAAH) inhibitor URB597 or CB1 receptor blockade by AM251 affected the following PCP-induced behavioural deficits reminiscent of schizophrenia-like symptoms: (1) working-memory impairment (cognitive deficit), (2) social withdrawal (negative symptom), and (3) hyperactivity in response to d-amphetamine challenge (positive symptoms). PCP-treated rats showed increased endocannabinoid levels in the nucleus accumbens and ventral tegmental area, whereas CB1 receptor expression and CP55,940-stimulated [35S]GTPgammaS binding were unaltered. URB597 reversed the PCP-induced social withdrawal but caused social withdrawal and working-memory deficits in saline-treated rats that were comparable to those observed after PCP treatment. Administration of AM251 ameliorated the working-memory deficit in PCP-treated rats, but impaired working memory in saline-injected controls. Taken together, these results suggest that FAAH inhibition may improve negative symptoms in PCP-treated rats but produce deleterious effects in untreated animals, possibly by disturbing endocannabinoid tone. A similar pattern (beneficial for schizophrenia-related cognitive deficits, but detrimental under normal conditions) accompanies CB1 receptor blockade.
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PMID:Inhibition of fatty-acid amide hydrolase and CB1 receptor antagonism differentially affect behavioural responses in normal and PCP-treated rats. 2889 60