Comparison of Acute and Repeated Phencyclidine Treatments in Mice as Pharmacological Models of Schizophrenia

Schizophrenia is a mental illness characterized by symptoms grouped in three categories, positive, negative/affective symptoms, and cognitive deficits. Despite its relevance, valid models of schizophrenia in mice are not well known. Thus, the main objective of the project was to determine whether the chronic treatment of mice with PCP could be a valid model of schizophrenia.  During the project, adult male C57BL/6 wild-type and 5-HT2AR knockout mice were used. They were treated subchronically either with phencyclidine (PCP) (10 mg/kg/day s.c.) or with a saline solution (10mg/kg/day). Behavioral studies such as the novel object recognition test (NOR), the tail suspension test (TST) and the study of the locomotor activity in an open field were conducted on the mice. To collect neurochemical data, the microdialysis technique was used and the resulting samples were analyzed in a high-performance liquid chromatography (HPLC). All the data obtained was analyzed using the appropriate statistical tests. The preliminary results of these procedures have shown that acute PCP administration significantly increased locomotor activity. However, no effects on short term memory measured in the NOR or negative symptomatology evaluated using the tail-suspension test were observed. On the contrary, repeated PCP administration induced a significant behavioral locomotor sensitization, cognitive deficits and mild depressive-like effects. Therefore, repeated PCP administration is more likely to resemble all the deficits of patients with schizophrenia. Thus, as this research shows, it can be a valid model of schizophrenia which will be useful in the development of new and effective antipsychotic drugs.