Mouse strain differences in phencyclidine-induced behavioural changes.

Different mouse strains show distinct behavioral responses to the psychosis-inducing drug phencyclidine (PCP). C57BL/6N, C57BL/6J, ddY, and ICR mice were compared. PCP caused greater hyperactivity and increased immobility in the forced swim test in ddY mice than in C57BL/6N and C57BL/6J, with ICR mice showing the least effect. However, no strain differences appeared in recognition memory impairment after chronic PCP withdrawal. These findings offer practical guidance for comparing genetic and drug-induced psychosis models in the C57BL/6 strain, which is commonly used in genetic studies, and suggest that strain differences may help identify biological mechanisms underlying PCP-induced behaviors relevant to major mental illnesses.

Study at a glance

Abstract

Administration of phencyclidine (PCP) is acknowledged to generate a model of psychosis in animals. With the identification of genetic susceptibility factors for schizophrenia and bipolar disorder, great efforts have been made to generate genetic animal models for major mental illnesses. As these disorders are multifactorial, comparisons among drug-induced (non-genetic) and genetic models are becoming an important issue in biological psychiatry. A major barrier is that the standard mouse strain used in the generation of genetic models is C57BL/6, whereas almost all studies with PCP-induced models have utilized other strains. To fill this technical gap, we systematically compared the behavioural changes upon PCP administration in different mouse strains, including C57BL/6N, C57BL/6J, ddY, and ICR. We observed strain differences in PCP-induced hyperlocomotion and enhanced immobility in the forced swim test (ddY>>C57BL/6N and 6J>ICR). In contrast, there was no strain difference in the impairment of recognition memory in the novel object recognition memory test after withdrawal of chronic PCP administration. This study provides practical guidance for comparing genetic with PCP-induced models of psychosis in C57BL/6. Furthermore, such strain differences may provide a clue to the biological mechanisms underlying PCP-induced endophenotypes possibly relevant to major mental illnesses.