Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 3, pp 335–346 | Cite as

Omega-3 fatty acids supplementation with lithium and aripiprazole for improving the balance of circulating hormones and brain neurotransmitters in manic mice model

Original Article


The present study was designed to evaluate the combined effect of lithium and aripiprazole supplemented with omega-3 fatty acids in methylphenidate (MPD)-induced manic mice. Swiss albino mice were administered with MPD or saline for 14 days, and based on changes in behavioral activities animals were treated with lithium, aripiprazole, and omega-3 fatty acids from the 8th day. Behavioral patterns were analyzed by video tracking. Thyroxine, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assayed in serum using ELISA kits. The levels of neurotransmitters in the whole brain were analyzed spectrofluorometrically. Glycogen synthase kinase 3β (GSK3β) mice brain mRNA expression levels and phosphorylated Akt (pAkt) protein levels were measured using RT-PCR and western blot, respectively. Results indicated that the administration of MPD alters the behavioral activity, thyroid hormones, FSH, LH, and testosterone levels. Lithium, aripiprazole, and omega-3 fatty acids alone significantly reduced MPD-induced behavior, hormonal, and neurotransmitter abnormalities. However, GSK3β and pAkt in the brain showed no significant differences in the level of expression. These results reveal that the combination of lithium and aripiprazole supplemented with omega-3 fatty acids provide protective effects against MPD-induced neuroendocrine system and multiple neurochemical abnormalities.


Mania Methylphenidate Open field test Thyroid hormone Dopamine Omega-3 fatty acids 



We wish to thank Annamalai University for the financial assistance with the award of a University Research Fellowship to Mr. P. Arunagiri.

Compliance with ethical standards

All experimental procedures were approved, and all the animals were cared for according to the Institutional Animal Ethics Committee of Rajah Muthiah Medical College and Hospital (Reg No. 160/1999/CPCSEA, Proposal number: 933) Annamalai Nagar Tamil Nadu, and India’s Animal Care Guidelines.

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai UniversityAnnamalainagarIndia
  2. 2.Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa

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