Differential affective behavioral outcomes in streptozotocin-induced diabetic mice: implications for pain-depression comorbidity research

Abstract

Diabetes mellitus is a highly prevalent chronic metabolic disorder associated with an elevated risk of diabetic-induced neuropathic pain and affective disturbances. However, animal models that recapitulate events of peripheral neuropathic pain and emotional alterations remain insufficiently characterized. This study aimed to investigate the association between hindpaw mechanical allodynia and distinct affective behavioral changes in a streptozotocin (STZ)-induced diabetic mouse model. Adult male C57BL/6 mice received a single intraperitoneal STZ injection (150 mg/kg), and body weight and blood glucose levels were monitored weekly for two weeks. Mechanical sensitivity was evaluated using von Frey filaments at baseline and at one and two weeks post-injection. Affective behaviors were assessed through the elevated plus maze (EPM), open field test (OFT), tail suspension test (TST), and marble burying test (MBT). STZ-treated mice developed sustained hyperglycemia and progressive weight loss. Furthermore, they displayed hindpaw mechanical allodynia since 1st week after injection. Although anxiety-like behavioral changes in the EPM were not prominent, STZ-treated mice exhibited reduced center-zone duration and locomotion in the OFT, along with fewer buried marbles in the MBT. Conversely, immobility time in the TST remained unchanged. These findings indicate that STZ-induced diabetic mice exhibit both peripheral mechanical hypersensitivity and selective depression-like behavioral alterations that differ across test paradigms, underscoring the need for diverse behavioral assessments when investigating diabetes-related pain-depression comorbidity.