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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
- Source :
- Psychopharmacology. 234(4)
- Publication Year :
- 2016
-
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.
- 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
Subjects
Details
- ISSN :
- 14322072
- Volume :
- 234
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....4e43b8c05a03d20ab884706d52f457fb