title: Nicotine evoked improvement in learning and memory is mediated through NPY Y1 receptors in rat model of Alzheimer's disease.
abstract: We investigated the role of endogenous neuropeptide Y (NPY) system in nicotine-mediated improvement of learning and memory in rat model of Alzheimer's disease (AD). Intracerebroventricular (icv) colchicine treatment induced AD-like condition in rats and showed increased escape latency (decreased learning), and amnesic condition in probe test in Morris water maze. In these rats, nicotine (0.5mg/kg, intraperitoneal), NPY (100 ng/rat, icv) or NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY (0.04 ng/rat, icv) decreased escape latency by 54.76%, 55.81% and 44.18%, respectively, on day 4 of the acquisition. On the other hand, selective NPY Y1 receptor antagonist, BIBP3226 (icv) produced opposite effect (44.18%). In the probe test conducted at 24h time point, nicotine, NPY or [Leu(31), Pro(34)]-NPY increased the time spent by 72.72%, 44.11% and 26.47%, respectively; while BIBP3226 caused reduction (8.82%). It seems that while NPY or [Leu(31), Pro(34)]-NPY potentiated, BIBP3226 attenuated the learning and memory enhancing effects of nicotine. Brains of colchicine treated rats showed significant reduction in NPY-immunoreactivity in the nucleus accumbens shell (cells 62.23% and fibers 50%), bed nucleus of stria terminalis (fibers 71.58%), central nucleus of amygdala (cells 74.33%), arcuate nucleus (cells 70.97% and fibers 69.65%) and dentate gyrus (cells 58.54%). However, in these rats nicotine treatment for 4 days restored NPY-immunoreactivity to the control level. We suggest that NPY, perhaps acting via NPY Y1 receptors, might interact with the endogenous cholinergic system and play a role in improving the learning and memory processes in the rats with AD-like condition.
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur 440 033, India.
authors.forename: Ritesh J
authors.initials: RJ
authors.lastname: Rangani
authors.forename: Manoj A
authors.initials: MA
authors.lastname: Upadhya
authors.forename: Kartik T
authors.initials: KT
authors.lastname: Nakhate
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
authors.forename: Nishikant K
authors.initials: NK
authors.lastname: Subhedar
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003078:Colchicine; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000187:drug effects; D007858:Learning / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C092926:BIBP 3226; D009478:Neuropeptide Y; D018722:Nicotinic Agonists; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D009538:Nicotine; D001120:Arginine; D003078:Colchicine