Effects of alpha-pinene on depressive behaviors in a dextromethorphan-induced depression model in rats

Depression, a multifactorial psychiatric disorder, affects millions of people worldwide and has limited effective therapeutic options. This study was aimed at investigating the potential antidepressant effects of alpha-pinene (aPI) in a dextromethorphan (DEX)-induced pharmacological model in rats.

Thirty-two adult male Wistar rats were randomly assigned to four groups (n = 8). The control group received the vehicle (DMSO diluted in saline, 0.5 mL/kg, IP) for 14 days. The model group was administered DEX (40 mg/kg, IP) for 14 days to induce neurobehavioral alterations associated with depressive-like states. Two treatment groups received alpha-pinene (5 or 10 mg/kg, IP), which was dissolved in DMSO diluted in saline and administered 30 min before DEX injection for 14 days. Behavioral assessments, including the sucrose preference test, tail suspension test, and forced swimming test, were conducted to evaluate depressive-like behaviors. Hippocampal levels of TNF-α and MDA were measured with ELISA to assess neuroinflammation and oxidative stress.

DEX administration resulted in significant depressive-like behaviors, as evidenced by increased immobility in the forced swimming test and tail suspension test, and decreased sucrose preference (P < 0.001). Treatment with alpha-pinene (5 and 10 mg/kg) significantly ameliorated these behavioral alterations (P < 0.05), and no significant difference was observed between doses. Additionally, DEX significantly elevated hippocampal TNF-α and MDA levels, whereas alpha-pinene treatment markedly decreased these levels (P < 0.05).

These findings suggest that alpha-pinene exerts antidepressant-like effects in a DEX-induced pharmacological model, potentially through modulation of neuroinflammatory and oxidative stress pathways. Nevertheless, confirmation in well-validated animal models of depression is required to strengthen the translational relevance of these findings.