Consequences of Long-Term Treatment with Agomelatine on Depressive-Like Behavior and Neurobiological Abnormalities in Pinealectomized Rats
| Autor: | Miroslava Stefanova, Jana Tchekalarova, Zlatina Nenchovska, L Alova, Lidia Kortenska, Milena Atanasova, Dimitrina Atanasova, Nikolai Lazarov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist Male medicine.medical_specialty Serotonin Time Factors medicine.drug_class medicine.medical_treatment Hippocampus Pinealectomy Melancholic depression Tritium Neuroprotection Pineal Gland Drug Administration Schedule Melatonin 03 medical and health sciences Behavioral Neuroscience Food Preferences 0302 clinical medicine Internal medicine Acetamides medicine Agomelatine Animals Hypnotics and Sedatives Rats Wistar Maze Learning Swimming Analysis of Variance Depressive Disorder Behavior Adaptation Ocular HPA axis Body Weight medicine.disease Rats 030104 developmental biology Endocrinology Exploratory Behavior Antidepressant Neuronal loss Psychology 030217 neurology & neurosurgery medicine.drug |
| Popis: | Previous data have shown that the rat model of melatonin deficit can cause a number of neurobiological aberrations. The aim of the present study was to determine whether the antidepressant drug agomelatine, a MT1/MT2 melatoninergic receptor agonist/5-HT2C receptor antagonist is able to prevent some of the behavioral, biochemical and cellular abnormalities induced by pinealectomy. The injection of agomelatine (40 mg/kg, i.p. for 5 weeks)/vehicle started after pinealectomy/sham procedure in Wistar rats. Animals were tested in different behavioral tests for anxiety and depression during the period of agomelatine treatment (chronic effect) and two months later (plastic effect). The effect of agomelatine on KCl-evoked serotonin (5-HT) release from the hippocampus, the activity of the hypothalamic-pituitary-adrenal (HPA) axis and neuronal loss in pinealectomized rats were assessed. Our results showed that agomelatine not only did not prevent the disturbed emotional arousal/anxiety behavior in pinealectomized rats during the treatment but the enhanced motor activity and decreased anxiety state was still observed two months after the discontinuation of treatment. However, the drug corrected a depressive-like behavior (chronic and plastic effect), alleviated the enhanced KCl-evoked 5-HT release in the hippocampus, recovered the suppressed negative feedback inhibition of HPA axis and exerted a neuroprotection in pinealectomized rats. Our findings suggest that pinealectomy can model melancholic depression disorder while the antidepressant action of agomelatine is associated with a correction of 5-HT release in the hippocampus, dysregulated HPA system and neuroprotection in limbic structures. |
| Databáze: | OpenAIRE |
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