Neurobehavioral manifestations in female rats after intermittent exposure to an anticancer agent, paclitaxel.

Abstract

Paclitaxel (PTX), a widely used chemotherapeutic agent, causes both peripheral and central neurotoxicity, leading to significant behavioral impairments. However, inadequate literature is available on PTX-induced neurobehavioral sequelae associated with anxiety, depression, and cognition in adults during and after chemotherapy. Therefore, the present study aimed to investigate neurobehavioral impairments in adult female rats following PTX exposure, with a specific focus on anxiety-like behaviors and cognitive functions such as learning and memory. In this study, we used adult female Wistar rats aged 10-12 weeks (average weight: 180 ± 5 g) and administered clinically relevant therapeutic doses of PTX (1.6 and 3.2 mg/kg body weight) intravenously once weekly for 6 weeks, simulating the clinical chemotherapy regimen. Neurobehavioral assessments were conducted after the first and sixth doses of PTX using validated mazes, including the photoactometer, open-field maze, elevated plus-maze (EPM; for anxiety-like behaviors), and the step-down latency test (SDL; for cognitive performance). Neurobehavioral patterns were recorded using autotracking software (ANY-maze, Stoelting Co., Wood Dale, Illinois, USA). Our findings revealed substantially reduced locomotor activity in the photoactometer, increased anxiety-like behaviors with amplified fear emotionality in the open-field and EPM tests, and memory impairment in the SDL test. These results suggest that the manifestation of anxiogenic and cognitive behavioral changes is associated with the administration of a higher dose (3.2 mg/kg) of PTX. In conclusion, our study indicates that PTX causes significant neurobehavioral impairments in rats after exposure to equivalent therapeutic doses of PTX.