Romanian Society of Pharmaceutical Sciences

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EXPERIMENTAL PHARMACOLOGICAL MODEL FOR INDUCING AND QUANTIFYING DEPRESSION IN MOUSE

SIMONA NEGREŞ1, CRISTINA ELENA ZBARCEA1*, ANDREEA ARSENE2, CORNEL CHIRIŢĂ1, ANCA BUZESCU1, BRUNO ŞTEFAN VELESCU1, EMIL ŞTEFĂNESCU1, OANA ŞEREMET1, FLORICA NICOLESCU3

Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Bucharest
1Department of Pharmacology and Clinical Pharmacy
2Department of Biochemistry
3Department of Toxicology

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Due to the fact that depression quantification in laboratory animals is hard to realize, an experimental study was conducted in order to create a model of depression induced by administration of reserpine in white male mice NMRI strain. To this end, three doses of reserpine were tested (0.5mg/kg-bw, 0.75 mg/kg-bw, 1.5 mg/kg-bw), a neurosympatholytic agent which produces catecholamine depletion at central and peripheral level. Depression onset evaluation was performed at 2 moments: after 11 and after 21 days of neurosympatholytic administration, both by classical pharmacological tests and also by determining the cerebral activity of monoamine oxidase (MAO), an enzyme involved in catecholamine catabolism. The experimental data revealed, after 21 days of treatment, for all doses used, modification of investigated parameters towards onset of depressive phenomenon. This way, compared to control group, for the animals submitted to forced swimming test, immobilizing time increased by more than 80% and MAO activity decreased dosedependently (-39.92% for 0.5 mg/kg-bw dose; -40.31% for 0.75 mg/kg-bw dose; -40.61% for 1.5 mg/kg-bw dose). These effects were in correlation with a significant reduction of motor activity. Making use of the created model (reserpine 0.75 mg/kg-bw, p.o., 21 days), antidepressant effect of clomipramine was determined as administered in 25 mg/kg-bw p.o. dose. Results were reproducible concerning the parameters used for depression evaluation in laboratory animals and clomipramine has normalized these parameters. It can be concluded that the model created can help to investigate the antidepressant effect of newly synthesized active substances.