Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
Motor control
Mood Disorders
Other disorders
Muscular system
Joints
Metabolism
Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
Q. Rainer, L. Xia, JP. Guilloux, C. Gabriel, DJ. David et al
Lab
Université Paris-Sud, Laboratoire Neuropharmacologie, Châtenay-Malabry, France.
Journal
International journal of neuropsychology
Abstract
Agomelatine (S20098) is a novel antidepressant drug with melatonergic agonist and 5-HT2C receptor antagonist properties, displaying antidepressant/anxiolytic-like properties in animal models and in humans. In a depression/anxiety-like mouse model in which the response of the HPA axis is blunted, we investigated whether agomelatine could reverse behavioural deficits related to depression/anxiety compared to the classical selective serotonin reuptake inhibitor, fluoxetine. Adult mice were treated for 8 wk with either vehicle or corticosterone (35 μg/ml.d) via drinking water. During the final 4 wk, animals were treated with vehicle, agomelatine (10 or 40 mg/kg i.p.) or fluoxetine (18 mg/kg i.p.) and tested in several behavioural paradigms and also evaluated for home-cage activity. Our results showed that the depressive/anxiety-like phenotype induced by corticosterone treatment is reversed by either chronic agomelatine or fluoxetine treatment. Moreover, agomelatine increased the dark/light ratio of home-cage activity in vehicle-treated mice and reversed the alterations in this ratio induced by chronic corticosterone, suggesting a normalization of disturbed circadian rhythms. Finally, we investigated the effects of this new antidepressant on neurogenesis. Agomelatine reversed the decreased cell proliferation in the whole hippocampus in corticosterone-treated mice and increased maturation of newborn neurons in both vehicle- and corticosterone-treated mice. Overall, the present study suggests that agomelatine, with its distinct mechanism of action based on the synergy between the melatonergic agonist and 5-HT2C antagonist properties, provides a distinct antidepressant/anxiolytic spectrum including circadian rhythm normalization.
BIOSEB Instruments Used:
Forced Swimming Test: New FST DUAL SENSOR (BIO-FST-DSM)
