Effects of alpha-pinene on depressive behaviors in a dextromethorphan-induced depression model in rats.
Danial Hasanisadr, Kaveh Rahimi, Zohreh Ghotbeddin
Journal of Taibah University Medical Sciences June 2, 2026 DOI: 10.1016/j.jtumed.2026.05.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | Adult male Wistar rats |
| Interventions | Alpha-pinene Dextromethorphan |
| Dose | Alpha-pinene 5 or 10 mg/kg; dextromethorphan 40 mg/kg |
| Duration | 14 days |
| Measures | Sucrose preference test, tail suspension test, forced swimming test, ELISA for TNF-alpha and MDA |
| Topics | Depression |
| Keywords | Rats Alpha-pinene Dextromethorphan Depressive behaviors |
| Key findings | Alpha-pinene at 5 and 10 mg/kg reduced depressive-like behaviors and lowered hippocampal TNF-alpha and MDA in dextromethorphan-treated rats, with no significant difference between the two doses. The authors propose these effects may involve modulation of neuroinflammatory and oxidative stress pathways, but note that confirmation in well-validated animal models of depression is needed. |
Abstract
Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
Comparable studies
Other preclinical and animal studies on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... | 2011 | Animal experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study |