title: Possible involvement of GABAergic and nitriergic systems for antianxiety-like activity of piperine in unstressed and stressed mice.
abstract: BACKGROUND
  An investigation was made to explore the possibility of anxiolytic activity of piperine in unstressed and stressed mice along with the underlying role of nitriergic and GABAergic modulation for the noted activity of piperine.
  
  
  METHODS
  Piperine (5, 10 and 20mg/kg, ip) was administered to unstressed mice. In another groups of animals, piperine was administered 30 min before subjecting them to immobilization stress for 6h. Antianxiety activity was evaluated by employing elevated plus maze, light-dark box and social interaction test. Diazepam was employed as standard anxiolytic drug.
  
  
  RESULTS
  Piperine produced significant antianxiety-like activity in unstressed and stressed mice. The anxiolytic-like activity of piperine was comparable to diazepam. In unstressed mice, piperine significantly increased brain GABA levels, but could not produce any change in plasma nitrite levels. Meanwhile, in stressed mice, piperine did not produce any significant change in GABA levels, but significantly decreased nitrite levels. Pre-treatment with aminoguanidine (50mg/kg, ip), an inducible nitric oxide synthase (NOS) inhibitor, significantly potentiated the anxiolytic-like activity of piperine, as compared to piperine and aminoguanidine alone in stressed mice. On the other hand, pretreatment with 7-nitroindazole (20mg/kg, ip), a neuronal NOS inhibitor significantly potentiated the antianxiety-like activity of piperine, as compared to piperine and 7-nitroindazole alone in unstressed mice.
  
  
  CONCLUSIONS
  These data suggest that the piperine produced significant anxiolytic activity in unstressed mice possibly through increase in GABA levels and inhibition of neuronal NOS. On the other hand, antianxiety activity in stressed mice might be through inhibition of inducible NOS.
authors.affiliation: Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, India. Electronic address: neerajmdu@rediffmail.com.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gilhotra
authors.affiliation: Department of Pharmaceutical Sciences, Guru Jambeshwar University of Science and Technology, Hisar, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Dhingra
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
chemical_list: D000470:Alkaloids; D014151:Anti-Anxiety Agents; D052117:Benzodioxoles; D006146:Guanidines; D007191:Indazoles; D009573:Nitrites; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D005680:gamma-Aminobutyric Acid; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D003975:Diazepam; C004479:pimagedine; C008922:piperine; C080122:7-nitroindazole
keywords: Anxiety; GABA; Inducible NOS; Neuronal NOS; Piperine