title: Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system.
abstract: Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a "social" cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an "empty" cage, and spent more time exploring a "novel" cage (i.e. new stimulus rat) versus a "familiar" cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003-0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Electronic address: alex.seillier@free.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Seillier
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giuffrida
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009812:Odorants; D010622:Phencyclidine / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000139:chemically induced* / Q000150:complications*; D012565:Schizophrenic Psychology; D012920:Social Behavior Disorders / Q000209:etiology*; D012938:Social Perception
chemical_list: D063385:Cannabinoid Receptor Modulators; D003511:Cyclohexanols; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D010622:Phencyclidine
keywords: Endocannabinoid; Odor discrimination; Phencyclidine; Social cognition