6-Methoxyflavone and donepezil behavioral plus neurochemical correlates in reversing chronic ethanol and withdrawal induced cognitive impairment

Arif, Mehreen, Rauf, Khalid, Rehman, Naeem Ur, Tokhi, Ahmed, Ikram, Muhammad and Sewell, Robert D. 2022. 6-Methoxyflavone and donepezil behavioral plus neurochemical correlates in reversing chronic ethanol and withdrawal induced cognitive impairment. Drug Design, Development and Therapy 16 , pp. 1573-1593. 10.2147/DDDT.S360677

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Abstract

Purpose: Chronic ethanol exposure causes neurotoxicity and long-term learning and memory impairment along with hippocampal and frontal cortical dysfunction. Flavonoids possess antioxidant and anti-inflammatory properties believed to be contributory factors in reversing cognitive decline. 6-Methoxyflavone (6-MOF), a flavonoid occurring naturally in medicinal plants, has been reported to instigate neuroprotection by reversing cisplatin-induced hyperalgesia and allodynia. Consequently, this study was designed to investigate 6-MOF activity in models of chronic ethanol-induced cognitive impairment along with neurochemical correlates. Methods: Mice were given ethanol orally (2.0 g/kg daily) for 24 days plus either saline, 6-MOF (25– 75mg/kg) or donepezil (4mg/kg) and then ethanol was withdrawn for the next 6 days. Animals were subsequently assessed for their cognitive performance in several models on days 1, 12, and 24, during abstinence (Day-26) and on the 7th day of the washout period. Following behavioral assessment, post-mortem dopamine, noradrenaline and vitamin C concentrations were quantified in the frontal cortex, hippocampus and striatum, using HPLC with UV detection. Results: Chronic ethanol treatment suppressed locomotor activity and impaired cognitive tasks, which included novel object recognition, performance in the Morris water maze as well as the Y-maze, socialization and nest-building behavior throughout the protocol and during withdrawal. These behavioral deficits were at least partially restored by the co-administration of 6-MOF or donepezil with ethanol as were ethanol-induced deficits in frontal cortical and hippocampal dopamine plus noradrenaline, together with striatal dopamine. 6-MOF co-administration with ethanol also modestly restored striatal vitamin C levels. Conclusion: It is postulated that, apart from donepezil, 6-MOF may be useful not only in the treatment of ethanol withdrawal severity but also in the management of chronic ethanol withdrawal induced cognitive impairment.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License
Publisher:	Dove Press
ISSN:	1177-8881
Date of First Compliant Deposit:	15 June 2022
Date of Acceptance:	9 May 2022
Last Modified:	10 May 2023 21:23
URI:	https://orca.cardiff.ac.uk/id/eprint/150534

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