Pharmacological benefits of agomelatine and vanillin in experimental model of Huntington's disease.
Huntington's disease (HD), a devastating neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss, depression. Melatonin receptors are widely expressed in the central nervous system. Vanilloids are also valuable as pharmacological tools for investigating neurobiology. This study investigates the utility of agomelatine, a dual agonist of MT₁ and MT₂ melatonin receptor as well as vanillin, a selective agonist of TRPV₁ (vanilloid receptor) in 3-nitropropionic acid (3-NPA) induced experimental HD in rats. Locomotor activity (Actophotometer), motor coordination (Rota rod) and learning-memory (Morris water maze) were assessed. Brain striatum oxidative stress (lipid peroxidation-MDA, glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), nitrosative stress (nitrite/nitrate) and mitochondrial enzyme complexes (I, II and IV) were also assessed. 3-NPA has induced weight loss, impaired locomotion, motor coordination as well as learning and memory. It has induced brain striatum oxidative as well as nitrosative stress, cholinergic dysfunction and impaired mitochondrial enzyme complexes (I, II and IV). Tetrabenazine (TBZ) was used as positive control. Treatment with agomelatine and vanillin and TBZ has significantly attenuated 3-NPA induced weight loss, impaired locomotion, motor coordination and learning-memory as well as biochemical impairments. Thus, agomelatine and vanillin exhibit protective effects against 3-NPA induced HD. It may be concluded that agomelatine and vanillin may provide benefits in HD.
Neuropharmacology Lab., Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab3@gmail.com.
Surbhi
S
Gupta
Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095 India. Electronic address: drbhupeshresearch@gmail.com.
Bhupesh
B
Sharma
D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000819:agonists*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000819:agonists*; D009281:Naphthalenes
D000081:Acetamides; D001547:Benzaldehydes; D008550:Melatonin; D009574:Nitro Compounds; D011422:Propionates; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C084711:agomelatine; D009281:Naphthalenes; C100058:vanillin; C015392:3-nitropropionic acid
3-Nitropropionic acid; Acetylcholinesterase; Mitochondrial enzyme complex; Morris water maze; Oxidative stress; Tetrabenazine