Abstract

ALLOSTATIC NEUROADAPTATIONS AND SYNAPTIC DYSREGULATION IN ETHANOL WITHDRAWAL SYNDROME: MECHANISMS AND THERAPEUTIC TARGETS

*Shivani Khandagale, Ankit Kediya, B. R. Gandhare, Rajashri Shinde, Rutuja Mind, Sandhya Jadhao

ABSTRACT

Ethanol withdrawal syndrome (EWS) is a neuropsychiatric condition that occurs following the abrupt cessation of chronic alcohol intake, characterized by anxiety, hyperexcitability, and seizures. The pathophysiology of EWS can be understood through the framework of Allostasis, where prolonged ethanol exposure induces neuroadaptive changes that become maladaptive during withdrawal. Chronic alcohol consumption disrupts synaptic balance by impairing GABAergic inhibition and enhancing glutamatergic excitability, leading to a hyperexcitable neural state. These alterations are associated with changes in Neuroplasticity and dysfunction of key brain circuits involved in reward and stress regulation. Additionally, increased Allostatic Load contributes to the severity of withdrawal symptoms. This review highlights the role of allostatic neuroadaptations and synaptic dysregulation in EWS and discusses emerging therapeutic strategies aimed at restoring neural homeostasis and improving clinical outcomes.

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