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Int. J. Mol. Sci. 2018, 19(7), 1973;

Abnormal Hippocampal Melatoninergic System: A Potential Link between Absence Epilepsy and Depression-Like Behavior in WAG/Rij Rats?

I.R.C.C.S. Neuromed, 86077 Pozzilli, Italy
Department of Physiology and Pharmacology, Sapienza University of Rome, 00161 Rome, Italy
Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
These authors contributed equally to this work.
Current address: Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova 16132, Italy and Department of Experimental Medicine, University of Genova, Genova 16132, Italy.
Author to whom correspondence should be addressed.
Received: 1 June 2018 / Revised: 4 July 2018 / Accepted: 5 July 2018 / Published: 6 July 2018
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Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings. However, neither pinealectomy nor melatonin administration had any effect on SWD incidence, suggesting that the melatoninergic system was not involved in the pathophysiology of absence-like seizures. Endogenous melatonin levels were lower in the hippocampus of WAG/Rij rats as compared to non-epileptic control rats, and this was associated with higher levels of melatonin receptors in the hippocampus, but not in the thalamus. In line with the reduced melatonin levels, cell density was lower in the hippocampus of WAG/Rij rats and was further reduced by pinealectomy. As expected, WAG/Rij rats showed an increased depression-like behaviour in the sucrose preference and forced swim tests, as compared to non-epileptic controls. Pinealectomy abolished the difference between the two strains of rats by enhancing depression-like behaviour in non-epileptic controls. Melatonin replacement displayed a significant antidepressant-like effect in both WAG/Rij and control rats. These findings suggest that a defect of hippocampal melatoninergic system may be one of the mechanisms underlying the depression-like phenotype in WAG/Rij rats and that activation of melatonin receptors might represent a valuable strategy in the treatment of depression associated with absence epilepsy. View Full-Text
Keywords: absence seizures; pinealectomy; depression; melatonin; MT receptors absence seizures; pinealectomy; depression; melatonin; MT receptors

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Moyanova, S.; De Fusco, A.; Santolini, I.; Celli, R.; Bucci, D.; Mastroiacovo, F.; Battaglia, G.; Nicoletti, F.; Tchekalarova, J. Abnormal Hippocampal Melatoninergic System: A Potential Link between Absence Epilepsy and Depression-Like Behavior in WAG/Rij Rats? Int. J. Mol. Sci. 2018, 19, 1973.

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