title: Evidence for the involvement of neuropeptide Y in the antidepressant effect of imipramine in type 2 diabetes.
abstract: Depression is a major comorbidity factor of diabetes and the outcome of one disorder influences the other. Our aim is to scrutinize the link between the two, if any. Since neuropeptide Y (NPY) system plays an important role in regulating central glucose sensing mechanisms, and also depression-related behavior, we test the involvement of NPY in the modulation of depression in type 2 diabetic mice. The mice were fed on high-fat diet and administered with low dose of streptozotocin to induce type 2 diabetes. These animals showed augmented plasma glucose and increased immobility time in tail suspension test (TST) suggesting induction of diabetes and depression. Intracerebroventricular (icv) treatment with NPY or NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY and intraperitoneal treatment with imipramine decreased immobility time. However, opposite effect was produced by NPY Y1 receptor antagonist BIBP3226 (icv). Moreover, reduced immobility time by imipramine was potentiated by NPY and [Leu(31), Pro(34)]-NPY, but attenuated by BIBP3226. Immunohistochemical analysis of the different nuclei of the extended amygdala, the region primarily involved in affective disorders, was undertaken. A significant reduction in NPY immunoreactivity in the central nucleus of amygdala, nucleus accumbens shell and lateral division of bed nucleus of stria terminalis of the diabetic mice was noticed; the response was ameliorated in imipramine treated animals. The results suggest that decreased NPY expression in the extended amygdala might be causally linked with the depression induced following type 2 diabetes and that the antidepressant action of imipramine in diabetic mice might be mediated by NPY-NPY Y1 receptor system.
authors.affiliation: Rungta College of Pharmaceutical Sciences and Research, Rungta Educational Campus, Kohka-Kurud Road, Bhilai 490024, Chhattisgarh, India.
authors.forename: Kartik T
authors.initials: KT
authors.lastname: Nakhate
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India.
authors.forename: Sadanand U
authors.initials: SU
authors.lastname: Yedke
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India.
authors.forename: Ashish P
authors.initials: AP
authors.lastname: Bharne
authors.affiliation: Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Near NCL, Pune 411021, Maharashtra, India.
authors.forename: Nishikant K
authors.initials: NK
authors.lastname: Subhedar
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, Maharashtra, India. Electronic address: kokaredada@yahoo.com.
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001786:Blood Glucose / Q000378:metabolism; D066274:Central Amygdaloid Nucleus / Q000378:metabolism; D003863:Depression / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012686:Septal Nuclei / Q000378:metabolism; D013311:Streptozocin
chemical_list: D000929:Antidepressive Agents, Tricyclic; C092926:BIBP 3226; D001786:Blood Glucose; D009478:Neuropeptide Y; C507698:Npy1r protein, mouse; D017476:Receptors, Neuropeptide Y; D013311:Streptozocin; D001120:Arginine; D007099:Imipramine
keywords: Depression; Diabetes; Imipramine; Neuropeptide Y; Streptozotocin