Volume 29, Issue 4 (December 2025)
Physiol Pharmacol 2025, 29(4): 464-475 |
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jahanabadi S, Safshekan P, Moradi A. Exploring the antidepressant-like effects of atorvastatin in ovariectomized mice: involvement of the nitric oxide pathway. Physiol Pharmacol 2025; 29 (4) :464-475
URL: http://ppj.phypha.ir/article-1-2388-en.html
URL: http://ppj.phypha.ir/article-1-2388-en.html
Abstract: (2122 Views)
Introduction: Atorvastatin, a lipid-soluble statin, is commonly used in managing high cholesterol levels and has been demonstrated to possess pleiotropic effects, such as antidepressant and neuroprotective properties. Women are more likely to suffer from depression because hormone levels change during ovariectomy and menopause. However, the role of statins in the treatment of ovariectomy-induced depressive behavior has not been adequately studied. We explored atorvastatin’s potential antidepressant effects as well as the potential function of the nitric oxide pathway in ovariectomized (OVX) mice.
Methods: Female mice underwent ovary removal, followed by administration of varying doses of atorvastatin alone or in conjunction with either a non-specific NO synthase inhibitor (L-NAME) or an NO precursor (L-arginine). Behavioral alterations were assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT), while hippocampal nitrite levels were also measured.
Results: One week post-procedure, OVX mice displayed a notably longer period of immobility in comparison to the sham group. OVX animals treated with atorvastatin (0.1 and 1 mg/kg) demonstrated antidepressant properties; additionally, OVX mice that received a sub effective dose of atorvastatin plus a sub-effective dose of L–NAME demonstrated pronounced antidepressant-like effects (P<0.05). L-arginine counteracted the antidepressant-like effects of a high dose of atorvastatin in OVX mice but did not affect their levels of locomotor activity in the OFT. Furthermore, atorvastatin administration prevented the increased hippocampal nitrite concentrations caused by ovariectomy (P<0.05).
Conclusion: The research revealed that atorvastatin exhibits significant antidepressant properties in OVX mice, potentially by suppressing the nitric oxide pathway.
Methods: Female mice underwent ovary removal, followed by administration of varying doses of atorvastatin alone or in conjunction with either a non-specific NO synthase inhibitor (L-NAME) or an NO precursor (L-arginine). Behavioral alterations were assessed using the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT), while hippocampal nitrite levels were also measured.
Results: One week post-procedure, OVX mice displayed a notably longer period of immobility in comparison to the sham group. OVX animals treated with atorvastatin (0.1 and 1 mg/kg) demonstrated antidepressant properties; additionally, OVX mice that received a sub effective dose of atorvastatin plus a sub-effective dose of L–NAME demonstrated pronounced antidepressant-like effects (P<0.05). L-arginine counteracted the antidepressant-like effects of a high dose of atorvastatin in OVX mice but did not affect their levels of locomotor activity in the OFT. Furthermore, atorvastatin administration prevented the increased hippocampal nitrite concentrations caused by ovariectomy (P<0.05).
Conclusion: The research revealed that atorvastatin exhibits significant antidepressant properties in OVX mice, potentially by suppressing the nitric oxide pathway.
Type of Manuscript: Experimental research article |
Subject:
Neurophysiology/Pharmacology
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