Howard C Becker1, Hugh Myrick, Lynn M Veatch. 1. Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Institute of Psychiatry, 67 President Street, Charleston, SC 29425, USA. beckerh@musc.edu
Abstract
AIMS: Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence. METHODS: Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites. RESULTS: Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice. CONCLUSIONS: Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification.
AIMS: Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence. METHODS: Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites. RESULTS: Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice. CONCLUSIONS: Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification.
Authors: Yusuf S Althobaiti; Farooq M Almutairi; Fahad S Alshehri; Ebtehal Altowairqi; Aliyah M Marghalani; Amal A Alghorabi; Walaa F Alsanie; Ahmed Gaber; Hashem O Alsaab; Atiah H Almalki; Alqassem Y Hakami; Turki Alkhalifa; Ahmad D Almalki; Ana M G Hardy; Zahoor A Shah Journal: Sci Rep Date: 2021-05-19 Impact factor: 4.379