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Involvement of D1 and D2 Dopamine Receptors in the Antidepressant-Like Effects of Selegiline in Maternal Separation Model of Mouse Publisher Pubmed



Amiri S1, 2 ; Aminikhoei H2, 3 ; Mohammadiasl A2, 3 ; Alijanpour S4 ; Hajmirzaian A2, 3 ; Rahimibalaei M5 ; Razmi A6 ; Olson CO1 ; Rastegar M1 ; Mehdizadeh M7 ; Zarrindast MR2
Authors
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Authors Affiliations
  1. 1. Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran
  5. 5. Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  6. 6. Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
  7. 7. Cellular and Molecular Research Center, Faculty of Advanced Technologies in Medicine, Department of Anatomical Sciences, Iran University of Medical Sciences, Tehran, Iran

Source: Physiology and Behavior Published:2016


Abstract

Mother-infant interactions are known to be associated with the psychological well-being of an individual in adulthood. It is well accepted that emotional stress in early life, such as maternal separation (MS), leads to alterations in the neurotransmission systems of various brain regions, especially the mesolimbic dopaminergic system, and subsequently can increase the risk for development of psychiatric disorders including depression in adulthood. Selegiline is an irreversible monoamine oxidase (MAO) type B inhibitor which increases striatal dopamine levels and exerts an antidepressant effect. In this study, 180 min of MS stress was applied to mice at postnatal day (PND) 2-14 followed by behavioral tests for determining depressive-like behaviors, such as forced swimming test (FST), splash test and sucrose preference test (SPT) in adult mice (PND 50). The open field test (OFT) also was applied to validate FST results. We used SCH23390 (D1 antagonist) and sulpiride (D2 antagonist) in order to determine the role of D1 and D2 dopamine receptors in antidepressant-like effects of selegiline. Our results revealed that MS provoked depressive-like behaviors in adult male mice, and the administration of selegiline attenuated depressive-like behaviors in MS mice. Our findings showed that D1 dopamine receptors facilitate the positive effects of selegiline on the passive behavior in the FST. Furthermore, antidepressant effects of selegiline on hedonic difficulties are mediated via D2 receptor in the SPT. The results of the splash test revealed that both D1 and D2 receptors mediate the protective effect of selegiline against motivational and self-care problems. Based on our results, we conclude that both D1 and D2 dopamine receptors are involved in mediating the antidepressant-like effect of selegiline. We found that D1 receptors mediate an effect on despair behavior, D2 receptors mediate an effect on anhedonia, and both D1 and D2 receptors contribute to the protective effects of selegiline on motivational complications. © 2016 Elsevier Inc.
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