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. 2013 Feb;225(3):531-42.
doi: 10.1007/s00213-012-2839-1. Epub 2012 Aug 19.

Chronic cannabinoid exposure reduces phencyclidine-induced schizophrenia-like positive symptoms in adult rats

Maria Sabrina Spano  1 , Liana Fattore, Francesca Cadeddu, Walter Fratta, Paola Fadda
Affiliations

Chronic cannabinoid exposure reduces phencyclidine-induced schizophrenia-like positive symptoms in adult rats

Maria Sabrina Spano et al. Psychopharmacology (Berl). 2013 Feb.

Abstract

Rationale: Chronic cannabis use can induce psychotic states that resemble schizophrenia. Yet, schizophrenic patients often smoke cannabis as a form of self-medication to counter the aversive symptoms of schizophrenia. We recently demonstrated an ameliorating effect of cannabinoid self-administration (SA) on negative and cognitive schizophrenia-like symptoms induced experimentally by the non-competitive N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). Whether cannabinoid SA alleviates or exacerbates schizophrenia-like positive symptoms is still unclear.

Objectives: This follow-up study aimed to evaluate the effect of self-administered cannabinoid on PCP-induced schizotypic positive symptoms in adult rats.

Methods: Male rats were trained to self-administer either the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN; 12.5 μg/kg/infusion) or its vehicle (Veh) intravenously. The effects of acute and chronic intermittent intraperitoneal administration of PCP (2.5 mg/kg) on motor parameters were then tested in Veh-SA and WIN-SA.

Results: Cannabinoid SA significantly attenuated the psychotomimetic effects of PCP exposure observed in control rats. Following acute PCP administration, WIN-SA animals displayed more frequent rearing and lower anxiety-like profile than Veh-SA rats. WIN-SA rats also exhibited lower behavioural sensitisation to chronic PCP treatment as demonstrated by reduced hyperlocomotion in response to an acute PCP challenge. In addition, parallel experiments performed in experimenter-administered rats that received WIN at comparable SA doses confirmed the ameliorating effects of cannabinoid exposure on PCP-induced schizotypic behaviours, indicating that motivational effects were not responsible for the ameliorative effects of cannabinoids.

Conclusions: Our results indicate that cannabis may exert protective effects on positive schizotypic symptoms in adult animals such as hypermotility and anxiety state.

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