title: Neuropeptide Y attenuates anxiety- and depression-like effects of cholecystokinin-4 in mice.
abstract: We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4)-evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY or antagonist BIBP3226, via intracerebroventricular route, and subjected to social interaction or forced swim test (FST) for the evaluation of anxiety- and depression-like phenotypes, respectively. To assess the interactions between the two systems, if any, NPYergic agents were administered prior to CCK-4 and the animals were subjected to these behavioral tests. Treatment with CCK-4 or BIBP3226 dose-dependently reduced social interaction time, while NPY or [Leu(31), Pro(34)]-NPY produced opposite effect. CCK-4 treatment increased immobility time in FST. This effect was reversed by NPY and [Leu(31), Pro(34)]-NPY, although BIBP3226 per se did not alter the immobility time. In a combination study, the anxiogenic or depressive effects of CCK-4 were attenuated by NPY or [Leu(31), Pro(34)]-NPY and potentiated by BIBP3226. The brains of CCK-4 treated rats were processed for NPY immunohistochemistry. Following CCK-4 treatment, the nucleus accumbens shell (AcbSh), ventral part of lateral division of the bed nucleus of stria terminalis (BSTLV), hypothalamic paraventricular nucleus and locus coeruleus showed a reduction in NPY-immunoreactive fibers. Population of NPY-immunopositive cells was also decreased in the AcbSh, BSTLV, prefrontal cortex and hypothalamic arcuate nucleus (ARC). However, NPY-immunoreaction in the fibers of the ARC and cells of the central nucleus of amygdala was unchanged. We conclude that, inhibition of NPY signaling in the brain by CCK-4 might be causal to anxiety- and depression-like behaviors.
authors.affiliation: Department of Anatomy & Cell Biology, University of Western Ontario, Ontario, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Desai
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440 033, Maharashtra, India.
authors.forename: C D
authors.initials: CD
authors.lastname: Borkar
authors.affiliation: Rungta College of Pharmaceutical Sciences and Research, Rungta Educational Campus, Kohka-Kurud Road, Bhilai 490 024, Chhattisgarh, India.
authors.forename: K T
authors.initials: KT
authors.lastname: Nakhate
authors.affiliation: Indian Institute of Science Education and Research (IISER), Central Tower, Sai Trinity Building, Garware Circle, Sutarwadi, Pashan, Pune 411 021, Maharashtra, India.
authors.forename: N K
authors.initials: NK
authors.lastname: Subhedar
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440 033, Maharashtra, India. Electronic address: kokaredada@yahoo.com.
authors.forename: D M
authors.initials: DM
authors.lastname: Kokare
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000378:metabolism*; D009483:Neuropsychological Tests; D011619:Psychotropic Drugs / Q000008:administration & dosage; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012919:Social Behavior; D013550:Swimming; D013758:Tetragastrin / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009478:Neuropeptide Y; C507698:Npy1r protein, mouse; D011619:Psychotropic Drugs; D017476:Receptors, Neuropeptide Y; D013758:Tetragastrin; D001120:Arginine
keywords: anxiety; cholecystokinin; depression; immunohistochemistry; neuropeptide Y