title: Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice.
abstract: In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain.
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: 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: Pankaj S
authors.initials: PS
authors.lastname: Kothavade
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: 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 / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001522:Behavior, Animal / Q000145:classification* / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002119:Calcium Carbonate; D004305:Dose-Response Relationship, Drug; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D007191:Indazoles; D009569:Nitric Oxide; D000376:Agmatine; D001120:Arginine; D002119:Calcium Carbonate; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester
keywords: Agmatine; Marble burring behaviour; Nitric oxide; Obsessive compulsive disorder