Chronic cannabinoid exposure reduces phencyclidine-induced schizophrenia-like positive symptoms in adult rats.
Source
CNR Neuroscience Institute, National Research Council, Monserrato (Cagliari), Italy.
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.
- PMID:
- 22903392
- [PubMed – indexed for MEDLINE]
Publication Types, MeSH Terms, Substances
Publication Types
MeSH Terms
- Animals
- Anxiety/chemically induced
- Anxiety/prevention & control
- Behavior, Animal/drug effects*
- Benzoxazines/administration & dosage
- Benzoxazines/therapeutic use
- Cannabinoid Receptor Agonists/administration & dosage
- Cannabinoid Receptor Agonists/therapeutic use
- Cannabinoids/administration & dosage
- Cannabinoids/therapeutic use*
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Hallucinogens/toxicity*
- Injections, Intravenous
- Male
- Morpholines/administration & dosage
- Morpholines/therapeutic use
- Motor Activity/drug effects
- Naphthalenes/administration & dosage
- Naphthalenes/therapeutic use
- Phencyclidine/toxicity*
- Rats
- Rats, Inbred Strains
- Schizophrenia/chemically induced
- Schizophrenia/prevention & control*
- Schizophrenic Psychology*
- Self Administration