Effects of Social Isolation on the Behavior of Wistar Rats Subjected to a Ketamine-Induced Model of Schizophrenia

Abstract This study aimed to evaluate the impact of chronic social isolation on the behavioral profile of male and female Wistar rats within a ketamine (Ket)-induced model of schizophrenia. A total of 144 adult Wistar rats (male and female) were divided into four experimental groups per sex: (1) Socialized + Saline (Sal) (Control group); (2) Socialized + Ket; (3) Isolated + Sal (Isolated group); (4) Isolated + Ket. Rats in the isolated groups were housed individually from postnatal day 60 (PND 60) for eight weeks. Ket (25 mg/kg, i.p.) was administered for seven consecutive days. Behavioral assessments included the open field test (OFT), elevated plus maze (EPM), and splash test (ST), and data were analyzed by three-way ANOVA (sex × isolation × Ket) followed by Tukey’s post hoc test. In the OFT, Ket increased locomotor activity in both sexes and reduced rearing, with this reduction being more pronounced in females. Isolation also reduced rearing. In the EPM, females spent more time in the open arms than males, and isolation was associated with reduced open-arm exploration only in females. In the ST, isolation increased the latency to initiate grooming and reduced the number of grooming events. No significant interaction between isolation and Ket was observed for any of the parameters analyzed. In conclusion, Ket and social isolation produced distinct and largely independent effects on behavioral domains relevant to schizophrenia, some of which were sex-dependent, and their combination did not yield a synergistic effect. These findings highlight the importance of including both sexes in the characterization of animal models relevant to schizophrenia.