title: Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex.
abstract: In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation.
  
  
  
  Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF2), and phosphorylated Erk1/2 (p-Erk1/2) levels in the dorsal or ventral hippocampus and in the medial prefrontal cortex.
  
  
  
  The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2 mg/kg Oxo, and unstressed group treated with Oxo. After 21 days of CRS, the groups were treated for 10 days with Oxo or saline. The anxiolytic role of Oxo was tested by using the following: forced swimming test, novelty suppressed feeding test, elevated plus maze test, and light/dark box test. The hippocampi and prefrontal cortex were used to evaluate BDNF and FGF2 protein levels and p-Erk1/2 levels.
  
  
  
  Oxo treatment significantly attenuated anxiety induced by CRS. Moreover, Oxo treatment counteracted the CRS-induced reduction of BDNF and FGF2 levels in the ventral hippocampus and medial prefrontal cerebral cortex CONCLUSIONS: The present study showed that Oxo treatment ameliorates the stress-induced anxiety-like behavior and rescues FGF2 and BDNF levels in two brain regions involved in CRS-induced anxiety, ventral hippocampal formation, and medial prefrontal cortex.
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Liberto
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Frinchi
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Verdi
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, 90134, Palermo, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Plescia
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, 90134, Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cannizzaro
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, 90134, Palermo, Italy.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Massenti
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy. giuseppa.mudo@unipa.it.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudò
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology* / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D018721:Muscarinic Agonists; D016222:Fibroblast Growth Factor 2; D010095:Oxotremorine
keywords: Anxiety; Behavioral test; Cerebral cortex; Chronic restraint stress; Elevated plus maze test; Forced swimming test; Neurotrophins; Novelty suppressed feeding test; mAChR