Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia

Social withdrawal in a rat model of schizophrenia is not caused by increased anxiety, according to this study. Rats treated with phencyclidine (PCP) spent less time in social interaction than controls but showed no anxiety-like behaviors in standard tests. Their social deficit was not reduced by repeated exposure to a familiar partner or by the anxiolytic diazepam, but was reversed by the cannabinoid agonist CP55,940, which has anxiogenic properties. The authors conclude that PCP-induced social withdrawal reflects primary negative symptoms (asociality) rather than secondary effects of anxiety, supporting the distinction between primary and secondary negative symptoms in schizophrenia.

Study at a glance

Abstract

Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.