The Effect of Zonisamide and Ethanol on Various Types of Memory in Rats

Abstract

Background: Antiepileptic drugs might be useful in the treatment of alcohol use disorder. One of these drugs is zonisamide, which has been found to decrease alcohol intake and cravings. An important structure in the pathophysiology of addiction is the hippocampus. Memory deficits, which frequently occur in alcoholics, are associated with ethanol-induced changes in hippocampal plasticity and neurogenesis. The aim of this study was to assess the potential protective effect of zonisamide on memory in rats receiving alcohol and after the discontinuation of its administration. Methods: Wistar rats (n = 43) were tested in four behavioral models, namely: Morris water maze (MWM), passive avoidance (PA), contextual fear conditioning (CFC), and cued fear conditioning (CuFC). Results: Zonisamide co-administered with ethanol impaired spatial memory in MWM, but the drug did not affect memory in PA. However, the beneficial effect of zonisamide was observed after the discontinuation of ethanol administration, which was associated with the improvement of associative memory in CFC and the alleviation of alcohol-induced locomotor disturbances in CuFC. Conclusion: Zonisamide has a differential influence on memory, which depends inter alia on type of the memory, length of ethanol administration, or its absence.

A Review of the Characteristics of Clinical Trials and Potential Medications for Alcohol Dependence: Data Analysis from ClinicalTrials.gov

“…In addition to enhancing the activity of GABA receptor systems, zonisamide may also reduce brain excitability by down-regulating GABA transporter proteins in the brain. A study conducted on rats found that treatment with zonisamide resulted in a significant reduction in ethanol consumption, as well as a differential influence on memory [ 99 ]. Additionally, another study conducted on mice found that zonisamide treatment led to a decrease in ethanol-induced conditioned place preference, suggesting a potential for the medication to reduce the rewarding effects of ethanol [ 92 ].…”