Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

Journal of Mind and Medical Sciences Volume 6 | Issue 2 Article 13 2019 Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice Cornel Chiriță Emil Ștefănescu Cristina E. Zbârcea Horațiu Mireșan Simona Negreș See next page for additional authors Follow this and additional works at: https://scholar.valpo.edu/jmms Part of the Behavioral Medicine Commons, Psychiatric and Mental Health Commons, and the Psychiatry Commons Recommended Citation Chiriță, Cornel; Ștefănescu, Emil; Zbârcea, Cristina E.; Mireșan, Horațiu; Negreș, Simona; Nuță, Diana C.; Limban, Carmen; Dănciulescu Miulescu, Rucsandra E.; and Marineci, Cristina D. (2019) "Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice," Journal of Mind and Medical Sciences: Vol. 6 : Iss. 2 , Article 13. DOI: 10.22543/7674.62.P261270 Available at: https://scholar.valpo.edu/jmms/vol6/iss2/13 This Research Article is brought to you for free and open access by ValpoScholar. It has been accepted for inclusion in Journal of Mind and Medical Sciences by an authorized administrator of ValpoScholar. For more information, please contact a ValpoScholar staff member at . Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice Authors Cornel Chiriță, Emil Ștefănescu, Cristina E. Zbârcea, Horațiu Mireșan, Simona Negreș, Diana C. Nuță, Carmen Limban, Rucsandra E. Dănciulescu Miulescu, and Cristina D. Marineci This research article is available in Journal of Mind and Medical Sciences: https://scholar.valpo.edu/jmms/vol6/iss2/13 https://scholar.valpo.edu/jmms/ https://proscholar.org/jmms/ ISSN: 2392-7674 J Mind Med Sci. 2019; 6(2): 261-270 doi: 10.22543/7674.62.P261270 Received for publication: February 17, 2019 Accepted: August 22, 2019 Research article Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice Cornel Chiriță1, Emil Ștefănescu1*, Cristina E. Zbârcea1, Horațiu Mireșan2, Simona Negreș1, Diana C. Nuță3, Carmen Limban3, Rucsandra E. Dănciulescu Miulescu4, Cristina D. Marineci1 1 Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacology and Clinical Pharmacy, Bucharest, Romania 2 Ovidius University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Toxicology, Constanța, Romania 3 Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Chemistry 4 Carol Davila University of Medicine and Pharmacy, Faculty of Dental Medicine, Department of Endocrinology Abstract The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test. Keywords  Highlights ✓ Selegiline plus doxepin double drug therapy increases significantly the antidepressant effect doxepin, selegiline, antidepressant, pharmacological research ✓ Selegiline plus doxepin double drug therapy prevents the sedative side effect of doxepin administered as a single drug therapy To cite this article: Chiriță C, Ștefănescu E, Zbârcea CE, Mireșan H, Negreș S, Nuță DC, Limban C, Dănciulescu Miulescu RE, Marineci CD. Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice. J Mind Med Sci. 2019; 6(2): 261-270. DOI: 10.22543/7674.62.P261270 *Corresponding author: Emil Ștefănescu, Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia Street, 020956, Bucharest, Romania E-mail: Cornel Chiriță et al. Introduction Depression is becoming a global problem due to the stress caused by the adaptation difficulties that our highspeed way of life currently demands (1). Mood disorders have been studied for decades and many theories have been proposed to explain the cause of depression. The original monoamine theory of depression suggested a direct involvement of the adrenergic system in the onset of this disorder (2). Later studies demonstrated a more complex relationship between the various endogenous neurotransmissions, suggesting an indirect role of the adrenergic system in depression as it modulates the function of other transmissions (3). The first significant breakthrough in the treatment of depressive disorders occurred 60 years ago with the approval of imipramine, thus opening a path for an entire class of drugs—tricyclic antidepressants—which act as nonselective noradrenergic and serotoninergic reuptake inhibitors (4). At the same time, compounds with other mechanisms such as monoamine oxidase inhibitors, enhanced the synaptic concentration of catecholamines and achieved similar positive effects on the symptoms of depression (5). Selegiline was created by Joseph Knoll almost 60 years ago and since then, it has been widely used for the treatment of Parkinson`s disease in low doses, Alzheimer`s disease, and major depression in higher doses (6). Selegiline acts in 3 ways: it reduces dopamine biotransformation through the inhibition of type B monoamine oxidase; it inhibits the dopamine reuptake; and it stimulates dopamine synthesis by blocking the presynaptic dopamine receptors (7). Although many therapeutic options are currently available, there are still cases of antidepressant-resistant depressions that require either new molecules (8-11) or new approaches in managing these disorders (12). Given that a new drug requires significant time and financial resources, combining existent therapies may prove to be a viable solution for treating complex atypical depressions. Materials and Methods A population of 70 white male NMRI mice having reached maturity and weighing 34 ± 6g was supplied by the rodent farm of “Carol Davila” University of Medicine and Pharmacy. Animals were kept in cages for 24 hours separately from other animals in order to reduce stress and ensure a gradual transition to the new environment. Later, they were housed in ventilated Plexiglas cages containing groups of 10 individuals with free access to food and water. Temperature and humidity were const (...truncated)