Social isolation is suggested to be a detrimental for the confusional states and abnormal interaction with cognitive impairment after the isoflurane plus surgery. However, the underlying mechanisms of these states remain unclear. After 2 hours exposure of isoflurane with abdominal surgery followed by social isolation for 24 h (ISO+SI-24h), the spontaneous alternations in Y-maze in male mice (7-10 weeks old) was significantly decreased, indicating that the spatial working memory was impaired by ISO+SI-24h. In general, only raring the 7-days of SI without the surgery, mice exhibit normal behaviors. However, the exposure of isoflurane with abdominal surgery in mice followed by raring 7 days of SI enhanced the mounting and sniffing behaviors against intruder mice in the home cage. In addition, the protein level of hippocampal dopamine D₂ receptors, but not prefrontal cortex was significantly decreased in mice with isoflurane plus surgery and SI. Since D₂ receptor is important for the cognitive function and psychosocial, these results imply the possibility that decrease in D₂ receptor contribute to the postoperative abnormal social interaction and cognitive dysfunction.