Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test.
Phencyclidine (PCP) induces stereotyped behaviour and social isolation in rats; comparisons with clinical observations have suggested that these behaviours may mimic certain aspects of the positive and the negative symptoms, respectively, of an acute schizophrenic episode. Novel antipsychotics are effective in treating the positive symptoms in schizophrenic patients and have also shown some promise in treating the negative symptoms. In the present study the effects of the novel antipsychotics remoxipride (2.5-20 mg/kg), risperidone (0.02-0.63 mg/kg), sertindole (0.01-2.5 mg/kg), olanzapine (0.16-2.5 mg/kg) and quetiapine (0.16-10 mg/kg) on PCP-induced behaviours were determined. The drugs were administered daily for 3 or 21 days in combination with vehicle or 2.0 mg/kg of PCP for the last 3 days of the administration regime, and the rats were tested using the social interaction test. The antipsychotic drugs all reliably reduced the level of PCP-induced stereotyped behaviour and had distinct effects on PCP-induced social isolation. Comparison with clinical findings suggests that the PCP-induced behaviours respond to treatment with antipsychotic drugs in a manner that correlates well with clinical observations, and that this animal model of schizophrenia may be useful for evaluating novel drug candidates. However, the study also showed that additional experiments are required to determine the specificity by which antipsychotic drugs alleviate PCP-induced behaviours because most of the drugs also affected considerably the behaviour of the control animals.
Sams-Dodd
F
F
H. Lundbeck A/S, Valby, Denmark.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001569:Benzodiazepines; D003987:Dibenzothiazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007398:Interpersonal Relations; D008297:Male; D000077152:Olanzapine; D010622:Phencyclidine / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000069348:Quetiapine Fumarate; D051381:Rats; D017208:Rats, Wistar; D017330:Remoxipride / Q000494:pharmacology; D012934:Social Isolation; D019956:Stereotypic Movement Disorder / Q000139:chemically induced* / Q000523:psychology
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D006213:Hallucinogens; D007093:Imidazoles; D007211:Indoles; D017330:Remoxipride; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D010890:Pirenzepine; C066304:sertindole; D010622:Phencyclidine; D000077152:Olanzapine