Anti-depressant effect of α-pinene on gonadectomized-related behavior in male rats

Document Type : Research Paper


1 Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran



Objective: This study aimed to determine anti-depressant effect of α-pinene on gonadectomized-related behavior in male rats.
Materials and Methods: Thirty adult male Wistar rats were assigned to 5 experimental groups. In the control group, surgeries were identical but testes were not clamped, ligated or excised. In the sham control, surgeries were identical with no treatment. In the imipramine group, rats were administered with imipramine (15 mg/kg) followed by castration for 2 weeks. In groups 4 and 5, following castration, rats were i.p. injected with 𝛼-pinene (0.5 and 1 mg/kg) for 2 weeks, respectively. Following recovery, forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed and serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activity were determined.
Results: According to the data, immobility time significantly increased following castration compared to control group (p<0.05). Administration of the imipramine significantly decreased immobility time compared to control group (p<0.05). Treatment with 𝛼-pinene (0.5 and 1 mg/kg) significantly decreased immobility time in comparison with sham control group (p<0.05). Number of crossings in the OFT significantly diminished following castration and treatment with 𝛼-pinene (0.5 and 1 mg/kg) increased number of crossings in the OFT compared to sham control group (P<0.05). Serum MDA significantly increased while SOD, GPX and CAT decreased following castration compared to the control group (p<0.05). Administration of the 𝛼-pinene (0.5 and 1 mg/kg) significantly improved serum MDA, SOD, GPX and CAT production compared to the sham rat (p<0.05).
Conclusion: These results suggested that 𝛼-pinene has anti-depressant and antioxidant effects in gonadectomized-related behavior in male rats


  1. Angermann CE, Ertl G. Depression, Anxiety, and Cognitive Impairment. Current Heart Failure Reports. 2018;15(6):398-410.
  2. Bangasser DA, Cuarenta A. Sex differences in anxiety and depression: circuits and mechanisms. Nature Reviews Neuroscience. 2021;22(11):674-84.
  3. Silva Almodóvar A, Nguyen D, Nahata MC. Evidence Needed for Efficacy of Antidepressant Medications Among Patients With Rheumatoid Arthritis. Annals of Pharmacotherapy. 2022:10600280211062271.
  4. Maheshwari N, Khan AA, Ali A, Mahmood R. Oral administration of pentachlorophenol impairs antioxidant system, inhibits enzymes of brush border membrane, causes DNA damage and histological changes in rat intestine. Toxicology Research. 2022.
  5. Ghosh S, Kumar A, Sachan N, Chandra P. Anxiolytic and antidepressant-like effects of essential oil from the fruits of Piper nigrum Linn.(Black pepper) in mice: involvement of serotonergic but not GABAergic transmission system. Heliyon. 2021 Apr 1;7(4):e06884.
  6. Yang H, Woo J, Pae AN, Um MY, Cho NC, Park KD, Yoon M, Kim J, Lee CJ, Cho S. α-Pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAA-benzodiazepine receptors. Molecular pharmacology. 2016 Nov 1;90(5):530-9.
  7. Ueno, H., Shimada, A., Suemitsu, S., Murakami, S., Kitamura, N., Wani, K., Matsumoto, Y., Okamoto, M., & Ishihara, T. (2020). Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy. IBRO Reports, 9,102-14.
  8. Türkez H, Aydın E. In vitro assessment of cytogenetic and oxidative effects of α-pinene. Toxicology and Industrial Health 2016; 32(1),168-76
  9. Goudarzi S, Rafieirad M. Evaluating the effect of α-pinene on motor activity, avoidance memory and lipid peroxidation in animal model of Parkinson disease in adult male rats. Research Journal of Pharmacognosy 2017; 4(2):53-63.
  10. Huh JS, Chung BH, Hong CH, Ryu JK, Kim JH, Han WK, et al. The effects of testosterone replacement on penile structure and erectile function after long-term castration in adult male rats. International journal of impotence research. 2018;30(3):122-8.
  1. Boivin JR, Piekarski DJ, Wahlberg JK, Wilbrecht L. Age, sex, and gonadal hormones differently influence anxiety-and depression-related behavior during puberty in mice. Psychoneuroendocrinology. 2017 Nov 1;85:78-87.
  2. Boissy A. Fear and fearfulness in animals. The quarterly review of biology. 1995 Jun 1;70(2):165-91.
  3. Ueno H, Takahashi Y, Murakami S, Wani K, Matsumoto Y, Okamoto M, et al. Effect of simultaneous testing of two mice in the tail suspension test and forced swim test. Scientific Reports. 2022;12(1):1-14.
  4. Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neuroscience & Biobehavioral Reviews. 2005 Jan 1;29(4-5):571-625.
  5. Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. European journal of pharmacology. 1998;350(1):21-9.
  6. Jung HJ, Shin HS. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome. wjmh. 2017;34(3):194-9.
  7. Drobisz D, Damborská A. Deep brain stimulation targets for treating depression. Behavioural brain research. 2019;359:266-73.
  8. Saeedipour S, Rafieirad M. Anti-anxiety effect of Alpha-pinene in comparison with Diazepam in adult male rats. Feyz 2020; 24 (3) :253-245
  9. Khan‐Mohammadi‐Khorrami MK, Asle‐Rousta M, Rahnema M, Amini R. Neuroprotective effect of alpha‐pinene is mediated by suppression of the TNF‐α/NF‐κB pathway in Alzheimer's disease rat model. Journal of Biochemical and Molecular Toxicology. 2022 May;36(5):e23006.
  10. Kuloglu M, Atmaca M, Tezcan E, Gecici Ö, Tunckol H, Ustundag B. Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder. Neuropsychobiology. 2002;46(1):27-32.
  11. Masuo Y, Satou T, Takemoto H, Koike K. Smell and Stress Response in the Brain: Review of the Connection between Chemistry and Neuropharmacology. Molecules. 2021 Jan;26(9):2571.
  12. Karthikeyan R, Kanimozhi G, Prasad NR, Agilan B, Ganesan M, Srithar G. Alpha pinene modulates UVA-induced oxidative stress, DNA damage and apoptosis in human skin epidermal keratinocytes. Life sciences. 2018 Nov 1;212:150-8.