title: Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer's disease.
abstract: Behavioral and Psychological Symptoms in Dementia (BPSD) are also seen in Alzheimer's disease (AD), being agitation and anxiety common symptoms. Since cholinergic agonists used to be the first pharmacological intervention in AD and this neurotransmission system have been related to cognitive and behavioral symptoms in this serious disease, we here address the question of a possible therapeutic role of PNU-282987 (PNU), an alpha7 nicotinic agonist, in motor activity and anxiety-like behaviors in an animal model of AD. On the other hand, since stress is an unavoidable condition in our daily activities, which activates physiological systems and deregulates body's homeostasis, we also evaluated the possible precipitating effects of stress in the onset of behavioral deficits in animals with susceptibility to AD. A dose of 0 or 1 mg/kg of PNU was administered to transgenic mice under restrained stress or not, resulting in 4 experimental groups: SAL, PNU, SAL-STR, PNU-STR. The main goal of this study was to evaluate the possible therapeutic role of PNU- 282987 alpha7 nicotinic agonist in motor activity and anxiety-like behaviors, as well as the possible effects of stress in precipitating the onset of behavioral deficits in animals with susceptibility to AD. The present results suggest a differential effect of stress (p=0.011) and PNU (p= 0.009) on anxiety evaluated in an open field depending on genetic vulnerability. Moreover, PNU seems to reverse stress effects in the same apparatus. This was also observed when a more sensitive task such as the zero maze was used.
authors.affiliation: Department of Psychology, Universitat Rovira i Virgili, 43007 Tarragona, Spain. paloma.vicens@urv.cat
authors.forename: Paloma
authors.initials: P
authors.lastname: Vicens
authors.forename: Diana
authors.initials: D
authors.lastname: Ribes
authors.forename: Luis
authors.initials: L
authors.lastname: Heredia
authors.forename: Margarita
authors.initials: M
authors.lastname: Torrente
authors.forename: José L
authors.initials: JL
authors.lastname: Domingo
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000628:therapy*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009069:Movement Disorders / Q000209:etiology / Q000628:therapy*; D009154:Mutation; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D053764:Presenilin-1 / Q000235:genetics; D012149:Restraint, Physical / Q000379:methods*
chemical_list: D016564:Amyloid beta-Protein Precursor; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D018722:Nicotinic Agonists; C498513:PNU-282987; C508853:PSEN1 protein, human; D053764:Presenilin-1