(+) MK-801 and phencyclidine induced neurotoxicity do not cause enduring behaviours resembling the positive and negative symptoms of schizophrenia in the rat.
Studies in rats and primates have demonstrated that repeated phencyclidine treatment can produce enduring cognitive deficits that may resemble the cognitive deficits seen in schizophrenia, suggesting that neurodegeneration resulting from NMDA-receptor dysfunction may be a valid model of schizophrenia. The purpose of the present experiments was to expand these findings and to determine if medium and high doses of the NMDA-antagonists phencyclidine and (+)MK-801 could produce permanent behavioural changes in animal tests with face validity for some aspects of the positive and negative symptoms of schizophrenia. Rats were treated with dose regimens of (+)MK-801 and phencyclidine known to produce mild and severe irreversible levels of neurotoxicity, and were tested 7 or 10 days after the last drug administration in the social interaction test and in standard activity cages. The rats did not show any enduring behavioural changes as a result of the treatment. The present study could therefore not provide additional evidence for the face validity of this model of schizophrenia.
Sams-Dodd
Frank
F
Pharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Frank.Sams-Dodd@bc.boehringer-ingelheim.com
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D010622:Phencyclidine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000209:etiology* / Q000503:physiopathology; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects
D016291:Dizocilpine Maleate; D010622:Phencyclidine