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
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.