1. 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
- Author
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Natale Belluardo, Valentina Di Liberto, Monica Frinchi, Maria Fatima Massenti, Carla Cannizzaro, Angela Vitale, Fulvio Plescia, Vincenzo Verdi, Giuseppa Mudò, Di Liberto, V., Frinchi, M., Verdi, V., Vitale, A., Plescia, F., Cannizzaro, C., Massenti, M., Belluardo, N., and Mudò, G.
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Elevated plus maze ,medicine.drug_class ,Behavioral test ,Prefrontal Cortex ,Hippocampal formation ,Anxiety ,Muscarinic Agonists ,Anxiolytic ,Hippocampus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Muscarinic acetylcholine receptor ,medicine ,Oxotremorine ,Muscarinic acetylcholine receptor M4 ,Animals ,Elevated plus maze test ,Rats, Wistar ,Prefrontal cortex ,mAChR ,Chronic restraint stre ,Forced swimming test ,Pharmacology ,Neurons ,Chemistry ,Brain-Derived Neurotrophic Factor ,Cerebral cortex ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Anti-Anxiety Agents ,Fibroblast Growth Factor 2 ,Chronic restraint stress ,Neurotrophins ,Novelty suppressed feeding test ,Neurotrophin ,Neuroscience ,030217 neurology & neurosurgery ,Stress, Psychological ,medicine.drug - Abstract
Rationale: 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. Objectives: 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. Methods: The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2mg/kg Oxo, and unstressed group treated with Oxo. After 21days of CRS, the groups were treated for 10days 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. Results: 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.
- Published
- 2016