title: Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators.
abstract: Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect. The present study investigated ability of agmatine to abolish the depressive-like behaviour induced by the administration of the lipopolysaccharide (LPS) in mice. Agmatine (20 and 40mg/kg) was administered daily for 7days, then the mice were challenged with saline or LPS (0.83mg/kg; i.p.) on the 7th day. After 24h of LPS administration we tested mice for depressive-like behaviour. LPS treated animals presented an increase in immobility time in the forced-swim test (FST), tail suspension test (TST) which was reversed by agmatine pre-treatment (20 and 40mg/kg). Oxidative/nitrosative stress evoked by LPS was ameliorated by both doses of agmatine in hippocampus (HC) and prefrontal cortex (PFC). Administration of LPS caused an increase in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas BDNF was down regulated in the HC. Agmatine pre-treatment at 40mg/kg ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β and TNF-α level. In addition, agmatine pre-treatment also up-regulated the BDNF level in the HC. The present study shows that pre-treatment of agmatine is able to abolish the behavioural responses in the FST and TST elicited by the LPS-induced model of depression that may depend on the inhibition of pro-inflammatory mediators, reduction of oxidative stress as well as activation neuroplasticity-related signalling in mice, suggesting that agmatine may constitute an monotherapy/adjuvant for the management of depression associated with inflammation.
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India. Electronic address: gawali.nit@gmail.com.
authors.forename: Nitin B
authors.initials: NB
authors.lastname: Gawali
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India.
authors.forename: Vipin D
authors.initials: VD
authors.lastname: Bulani
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India.
authors.forename: Amrita A
authors.initials: AA
authors.lastname: Chowdhury
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India.
authors.forename: Padmini S
authors.initials: PS
authors.lastname: Deshpande
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India.
authors.forename: Dnyaneshwar M
authors.initials: DM
authors.lastname: Nagmoti
authors.affiliation: Pharmacology Research Lab 1, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (E), Mumbai 400019, India. Electronic address: juvekar.archana@gmail.com.
authors.forename: Archana R
authors.initials: AR
authors.lastname: Juvekar
mesh_terms: D000376:Agmatine / Q000008:administration & dosage*; D000818:Animals; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D015538:Nitrosation / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D000376:Agmatine
keywords: Agmatine; BDNF; Depressive-like behaviour; Lipopolysaccharide; Oxidative stress; Pro-inflammatory cytokines