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Glatiramer acetate attenuates depressive/anxiety-like behaviors and cognitive deficits induced by post-weaning social isolation in male mice

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Abstract

Rationale

Major depressive disorder (MDD) is a debilitating disorder with adverse effects on mood, memory, and quality of life.

Objectives

In this study, the antidepressant potential of glatiramer acetate (GA), a drug used in the management of multiple sclerosis, was investigated in acute and chronic models of depression in male mice. The acute antidepressant screening was performed with the forced swim (FST) and tail suspension (TST) tests. In the chronic phase, post-weaning social isolation (SI) was used to induce depressive-/anxiety-like behaviors.

Methods

Mice were reared in two different groups of social (SG) and isolated (IG) for 4 weeks. IG mice were treated with 0.5, 1.0, and 2.0 mg/kg of GA for the last 2 weeks of the SI period. Animals were assessed by the behavioral tests of depression, anxiety, learning, and memory, and hippocampal brain-derived neurotrophic factor (BDNF) level was measured.

Results

The acute tests confirmed the antidepressant potential of GA. In the chronic phase, GA could reduce immobility time in FST (P < 0.05), increase exploration activity in open field test (P < 0.05), increase open arms duration (P < 0.05) and entries in elevated plus maze (P<0.001), and improve memory and learning in passive avoidance test (P < 0.05). The BDNF level was increased in IG mice and decreased in IG mice treated with GA.

Conclusions

Our results showed that GA improved depressive-/anxiety-like behaviors and cognitive dysfunction of SI reared mice without increasing the BDNF level which may be associated with other mechanisms of actions of GA.

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Acknowledgments

We thank Ms. PM. Saffari and Mrs. G. Ghamami for the technical help in conducting laboratory tests. We thank Tofigh Daru Company for providing us with Glatiramer acetate.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Sanusi Andah Salihu, Homanaz Ghafari, Narges K. Gortany, Hamed Shafaroodi & Mahmoud Ghazi-Khansari

  2. Department of Pharmacodynamics and Toxicology, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahnaz Ahmadimanesh

  3. Food and Drug Control Laboratory, Food and Drug Vice Presidency, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahnaz Ahmadimanesh

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  1. Sanusi Andah Salihu
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  2. Homanaz Ghafari
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Salihu, S.A., Ghafari, H., Ahmadimanesh, M. et al. Glatiramer acetate attenuates depressive/anxiety-like behaviors and cognitive deficits induced by post-weaning social isolation in male mice. Psychopharmacology 238, 2121–2132 (2021). https://doi.org/10.1007/s00213-021-05836-5

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