Abstract

EXPLORING MORIN AS A TREATMENT FOR KINDLINGASSOCIATED POST-ICTAL DEPRESSION IN RATS

Nita B. Vasaikar*, Monika J. Suryavanshi and Shantvan S. Salunke

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Abstract

Epilepsy, a chronic neurological disorder marked by recurrent seizures, is often accompanied by postictal depression, significantly affecting patient quality of life. In this study, we evaluated the pharmacological effects of morin, a bioflavonoid, on kindling-associated postictal depression in a PTZ-induced kindling model in rats. Morin was administered orally at doses of 10, 20, and 40 mg/kg. Several in-vivo parameters were assessed, including body weight, onset of convulsion, duration of clonic and tonic convulsions, seizure severity scoring, and behavioral assessments via the open field test and tail suspension test. The results indicated that morin administration had a protective effect against the typical weight loss observed with PTZ-induced seizures. It significantly delayed the onset of convulsions, suggesting anticonvulsant properties. Additionally, morin reduced the duration of both clonic and tonic convulsions in a dose-dependent manner, with higher doses showing more pronounced effects. Seizure severity scores were also significantly lower in morin-treated groups compared to controls. Behavioral assessments revealed that morin-treated rats exhibited increased total locomotor activity in the open field test, indicating a reduction in depressive-like behaviors. In the tail suspension test, morin significantly reduced the duration of immobility, further supporting its antidepressant effects. Ex-vivo analyses focused on oxidative stress markers, neurotransmitter levels, and neuronal enzyme activities in the brain. Morin treatment resulted in decreased levels of oxidative stress markers such as malondialdehyde (MDA) and nitric oxide, while significantly increasing antioxidant levels, including superoxide dismutase (SOD) and glutathione (GSH). Brain dopamine levels were elevated in morin-treated groups, correlating with improved mood and motor functions. Morin also increased brain GABA levels, contributing to its anticonvulsant and anxiolytic effects, and enhanced serotonin (5- HT) levels, supporting its role in reducing depressive symptoms. Furthermore, morin improved Na-K-ATPase and Ca-ATPase activity, indicating better neuronal function and stability. In conclusion, morin demonstrated significant anticonvulsant and antidepressant effects in PTZ-kindled rats, mediated through a combination of antioxidant mechanisms, neurotransmitter modulation, and enhanced neuronal enzyme activities. These findings suggest that morin could be a promising therapeutic agent for managing epilepsy and the associated postictal depression, providing a multifaceted approach to treatment.

Keywords: Epilepsy, Postictal depression, Morin, Pentylenetetrazole (PTZ) kindling, Anticonvulsant, Neurotransmitter modulation, Oxidative stress.