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Anxiolytic- and Antidepressive-Like Effects of Harmaline in Mice Are Mediated Via Histamine H3 Receptor Blockade Publisher Pubmed



Khakpai F1 ; Golshani SP2 ; Alijanpour S3 ; Ebrahimighiri M4 ; Zarrindast MR2, 5
Authors
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Authors Affiliations
  1. 1. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran
  4. 4. Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran
  5. 5. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

Source: Biochemical and Biophysical Research Communications Published:2024


Abstract

Many neuropsychiatric disorders can be caused by neurotransmitter dysfunction. Experimental studies have demonstrated that histamine and the harmaline affect physiological processes through interaction with other neurotransmitter systems. The objective of these experiments was to investigate the involvement of the histaminergic system in the effects of harmaline on anxiety- and depressive-related effects in male NMRI mice. Behavioral tests were employed to evaluate anxiety-related symptoms (elevated plus maze; EPM), depressive-like symptoms (forced swim test; FST), and cognitive decline (step-down test). The histamine H3 receptor (H3R) agonist α-methylhistamine dihydrobromide (α-MH; 5 mg/kg, i.p.) had anxiolytic- and depressive-like effects, while the H3R antagonist thioperamide (10 mg/kg, i.p.) showed an antidepressive-like property. The subthreshold dose of α-MH resulted in an increase in the tendency of mice treated with the harmaline (2.5 mg/kg) to remain in the EPM open-arms. A subthreshold dose of thioperamide (5 mg/kg) increased the time spent in the open-arms in mice treated with harmaline (2.5 and 5 mg/kg) while a high dose of harmaline decreased the immobility time. Furthermore, two higher doses of harmaline resulted in a reduction in the number of open-arm entries. Similarly, mice administered with thioperamide and a low dose of harmaline decreased locomotor activity in the EPM. Ultimately, the combined thioperamide and harmaline did not impair memory retrieval of mice. These experiments demonstrate that the histaminergic system is implicated in the anxiety- and depressive-related effects of harmaline. The combination of thioperamide and harmaline is effective in treating anxiety and depression without having an adverse effect on memory formation. © 2024 Elsevier Inc.
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