• KukuiaKennedy Kwami EdemKKEDepartment of Medical Pharmacology, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana. Electronic address: kkekukuia@ug.edu.gh., BurnsFrederick BoakyeFBDepartment of Pharmacology & Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, P.O Box LG 43, Legon, Accra, Ghana. Electronic address: fbboakye001@st.ug.edu.gh., Adutwum-OfosuKevin KofiKKDepartment of Anatomy, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana. Electronic address: kadutwum-ofosu@ug.edu.gh., Frimpong Appiah, Seth Kwabena Amponsah, Richard Begyinah, KoomsonAwo EfuaAEDepartment of Medical Pharmacology, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana. Electronic address: aekoomson@ug.edu.gh., Yaw Takyi Ferka, TagoeThomas AmateyTADepartment of Physiology, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana. Electronic address: tatagoe@ug.edu.gh., and Patrick Amoateng.
• Department of Medical Pharmacology, College of Health Sciences, University of Ghana, Korle Bu, Accra, Ghana. Electronic address: kkekukuia@ug.edu.gh.
• Neuroscience. 2023 May 21; 519: 9010690-106.

AbstractIron supplementation previously demonstrated antidepressant-like effects in post-partum rats. The present study evaluates the possible synergistic antidepressant effect of sub-therapeutic dose of iron co-administered with citalopram or imipramine in female Institute of Cancer Research mice. Depression-like symptoms were induced in the forced swim (FST), tail suspension (TST), and open space swim (OSST) tests while open field test (OFT) was used to assess locomotor activity. Mice (n = 8) received iron (0.8-7.2 mg/kg), citalopram (3-30 mg/kg), imipramine (3-30 mg/kg), desferrioxamine (50 mg/kg) or saline in the single treatment phase of each model and subsequently a sub-therapeutic dose of iron co-administered with citalopram or imipramine. Assessment of serum brain derived neurotrophic factor (BDNF) and dendritic spine density was done using ELISA and Golgi staining techniques respectively. Iron, citalopram and imipramine, unlike desferrioxamine, reduced immobility score in the TST, FST and OSST without affecting locomotor activity, suggesting antidepressant-like effect. Sub-therapeutic dose of iron in combination with citalopram or imipramine further enhanced the antidepressant-like effect, producing a more rapid effect when compared to the iron, citalopram or imipramine alone. Iron, citalopram and imipramine or their combinations increased serum BDNF concentration, hippocampal neuronal count and dendritic spine densities. Our study provides experimental evidence that iron has antidepressant-like effect and sub-therapeutic dose of iron combined with citalopram or imipramine produces more rapid antidepressant-like effect. We further show that iron alone or its combination with citalopram or imipramine attenuates the neuronal loss associated with depressive conditions, increases dendritic spines density and BDNF levels. These finding suggest iron-induced neuronal plasticity in the mice brain.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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