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

Verdi, V.; Vitale, A.; Mudò, G.

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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 0.2 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. 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.
Lingua originaleEnglish
pagine (da-a)559-573
Numero di pagine15
RivistaPsychopharmacology
Volume234
Stato di pubblicazionePublished - 2017

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Oxotremorine
Cholinergic Agonists
Brain-Derived Neurotrophic Factor
Anti-Anxiety Agents
Muscarinic Receptors
Fibroblast Growth Factor 2
Prefrontal Cortex
Hippocampus
Anxiety
Neuronal Plasticity
Cerebral Cortex
Nerve Growth Factors
Depressive Disorder
Transcriptional Activation
Antidepressive Agents
Depression

All Science Journal Classification (ASJC) codes

  • Pharmacology

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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 = "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 0.2 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. 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.",
keywords = "Anxiety; Behavioral test; Cerebral cortex; Chronic restraint stress; Elevated plus maze test; Forced swimming test; mAChR; Neurotrophins; Novelty suppressed feeding test; Pharmacology",
author = "{Verdi, V.; Vitale, A.; Mud{\`o}, G.} and Massenti, {Maria Fatima} and Natale Belluardo and Giuseppa Mudo' and Carla Cannizzaro and Fulvio Plescia and {Di Liberto}, Valentina and Monica Frinchi",
year = "2017",
language = "English",
volume = "234",
pages = "559--573",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - 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

AU - Verdi, V.; Vitale, A.; Mudò, G.

AU - Massenti, Maria Fatima

AU - Belluardo, Natale

AU - Mudo', Giuseppa

AU - Cannizzaro, Carla

AU - Plescia, Fulvio

AU - Di Liberto, Valentina

AU - Frinchi, Monica

PY - 2017

Y1 - 2017

N2 - 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 0.2 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. 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.

AB - 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 0.2 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. 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.

KW - Anxiety; Behavioral test; Cerebral cortex; Chronic restraint stress; Elevated plus maze test; Forced swimming test; mAChR; Neurotrophins; Novelty suppressed feeding test; Pharmacology

UR - http://hdl.handle.net/10447/226079

UR - https://link.springer.com/article/10.1007%2Fs00213-016-4498-0

M3 - Article

VL - 234

SP - 559

EP - 573

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

ER -