title: Neurokinin3-R agonism in aged rats has anxiolytic-, antidepressant-, and promnestic-like effects and stimulates ACh release in frontal cortex, amygdala and hippocampus.
abstract: Neurokinin-3 receptors (NK(3)-R) are localized in brain regions which have been implicated in processes governing learning and memory as well as emotionality. The effects of acute subcutaneous (s.c.) senktide (0.2 and 0.4 mg/kg), a NK(3)-R agonist, were tested in aged (23-25 month old) Wistar rats: (a) in an episodic-like memory test, using an object discrimination task (this is the first study to test for deficits in episodic-like memory in aged rats, since appropriate tests have only recently became available); (b) on parameters of anxiety in an open field test, (c) on indices of depression in the forced swimming test and (d) on the activity of cholinergic neurons of the basal forebrain, using in vivo microdialysis and HPLC. Neither the saline-, nor senktide-treated aged animals, exhibited episodic-like memory. However, the senktide-, but not the vehicle-treated group, exhibited object memory for spatial displacement, a component of episodic memory. Senktide injection also had anxiolytic- and antidepressant-like effects. Furthermore, the active doses of senktide on behavior increased ACh levels in the frontal cortex, amygdala and hippocampus, suggesting a relationship between its cholinergic and behavioral actions. The results indicate cholinergic modulation by the NK(3)-R in conjunction with a role in the processing of memory and emotional responses in the aged rat.
authors.affiliation: Center for Behavioral Neuroscience, Heinrich-Heine-University of Düsseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schäble
authors.forename: B
authors.initials: B
authors.lastname: Topic
authors.forename: T
authors.initials: T
authors.lastname: Buddenberg
authors.forename: D
authors.initials: D
authors.lastname: Petri
authors.forename: J P
authors.initials: JP
authors.lastname: Huston
authors.forename: M A
authors.initials: MA
authors.lastname: de Souza Silva
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013550:Swimming
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018678:Cholinergic Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D000109:Acetylcholine