ENHANCEMENT OF IMMOBILITY IN A FORCED SWIMMING TEST BY SUBACUTE OR REPEATED TREATMENT WITH PHENCYCLIDINE - A NEW MODEL OF SCHIZOPHRENIA

Citation
Y. Noda et al., ENHANCEMENT OF IMMOBILITY IN A FORCED SWIMMING TEST BY SUBACUTE OR REPEATED TREATMENT WITH PHENCYCLIDINE - A NEW MODEL OF SCHIZOPHRENIA, British Journal of Pharmacology, 116(5), 1995, pp. 2531-2537
Citations number
77
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
116
Issue
5
Year of publication
1995
Pages
2531 - 2537
Database
ISI
SICI code
0007-1188(1995)116:5<2531:EOIIAF>2.0.ZU;2-E
Abstract
1 Immobility induced by forced swimming is well known as an animal mod el of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect o f phencyclidine (PCP) on immobility in the forced swimming test was in vestigated in mice, since PCP produces such negative symptoms in human s. 2 Repeated treatment with PCP (10 mg kg(-1) day(-1), s.c., once a d ay for 14 days) prolonged the immobility time in the forced swimming t est 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg( -1), s.c.), or by repeated treatment with methamphetamine (0.5 and 1 m g kg(-1) day(-1), s.c., once a day for 14 days). 3 The enhancing effec t of PCP (10 mg kg(-1) day(-1), s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4 Haloperidol (0.3 and 1 mg kg(-1), p.o.), ritanserin (3 and 10 mg kg(-1), p.o.), risperi done (0.1-1 mg kg(-1) p.o.), and clozapine (3 and 10 mg kg(-1), p.o.) failed to attenuate the immobility induced by the forced swimming in m ice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg(-1)) and clozapine (30 mg kg(-1)) did attenuate this immobility. 5 The enha ncing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg(-1) p.o.), risperidone (0.3 mg kg(-1), p.o.), and clozapi ne (3 and 10 mg kg(-1), p.o.), whereas haloperidol (0.3 and 1 mg kg(-1 ), p.o.) had no effect. 6 These results suggest that the enhancement o f immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particul arly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.