Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia

Y. Noda, K. Yamada, H. Furukawa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. Repeated treatment with PCP (10 mg kg−1 day−1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 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 mg kg−1 day−1, s.c., once a day for 14 days). The enhancing effect 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. Haloperidol (0.3 and mg kg−1, p.o.), ritanserin (3 and 10 mg kg−1, p.o.), risperidone (0.1‐1 mg kg, p.o.), and clozapine (3 and 10 mg kg−1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice 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. The enhancing 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 clozapine (3 and 10 mg kg−1, p.o.), whereas haloperidol (0.3 and 1 mg kg−1, p.o.) had no effect. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5‐HT2A receptors. 1995 British Pharmacological Society

Original languageEnglish
Pages (from-to)2531-2537
Number of pages7
JournalBritish Journal of Pharmacology
Volume116
Issue number5
DOIs
Publication statusPublished - 01-01-1995

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Phencyclidine
Schizophrenia
Ritanserin
Clozapine
Risperidone
Haloperidol
Depression
Therapeutics
Animal Models
Methamphetamine
Pharmaceutical Preparations
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia",
abstract = "Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. Repeated treatment with PCP (10 mg kg−1 day−1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 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 mg kg−1 day−1, s.c., once a day for 14 days). The enhancing effect 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. Haloperidol (0.3 and mg kg−1, p.o.), ritanserin (3 and 10 mg kg−1, p.o.), risperidone (0.1‐1 mg kg−, p.o.), and clozapine (3 and 10 mg kg−1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice 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. The enhancing 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 clozapine (3 and 10 mg kg−1, p.o.), whereas haloperidol (0.3 and 1 mg kg−1, p.o.) had no effect. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5‐HT2A receptors. 1995 British Pharmacological Society",
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Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine : a new model of schizophrenia. / Noda, Y.; Yamada, K.; Furukawa, H.; Nabeshima, Toshitaka.

In: British Journal of Pharmacology, Vol. 116, No. 5, 01.01.1995, p. 2531-2537.

Research output: Contribution to journalArticle

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