The effect of zonisamide on memory processes - A preclinical study.

OBJECTIVE: Zonisamide is an antiepileptic drug with a perspective of a broader use. Although it is regarded as a relatively safe drug, zonisamide might cause disorders of the central nervous system. The study assessed the influence of zonisamide on spatial and emotional memory in adult Wistar rats. METHODS: Morris water maze test was used to examine the effect of zonisamide administered p.o. as single dose (50 mg/kg or 100 mg/kg) or repeatedly (50 mg/kg) on spatial memory. The impact of zonisamide administered as above on emotional memory was assessed in the Passive avoidance test. RESULTS: Zonisamide mainly in a high acute dose impaired the spatial memory, whereas when administered repeatedly, its effect was observed only in the initial phase of the study. Emotional memory disturbances were noted only during repeated administration of zonisamide. CONCLUSION: Zonisamide may impair memory and learning processes in rats but the results are varied and depend on the type of memory.

Can the Impact of Topiramate on Memory Processes be Related to Its 'Antialcoholic Activity'?-A Preclinical Study.

AIMS: Topiramate causes the inhibition of alcohol consumption in addicts but the mechanism of this action has not been fully understood yet. Nowadays, it seems that memory may have a role in the development of dependence. In this study, the impact of topiramate and ethanol on the bioelectric activity of the brain in rabbits and on spatial memory in rats was evaluated. SHORT SUMMARY: The aim of the study was to assess the effect of co-administration of topiramate and ethanol on bioelectric activity of the rabbits' brain and on spatial memory in rats. Topiramate decreased ethanol-induced changes in all studied brain structures and improved memory and learning processes. METHODS: A pharmaco-electroencephalography study was used to examine the effect of topiramate (25 mg/kg/day) co-administered for 6 weeks with ethanol on the bioelectric activity of the rabbits' brain. The influence of the drug was also assessed in first and second weeks of the abstinence period. Spatial memory was evaluated in rats using Morris water maze task. Topiramate (60 mg/kg/day) was administered with the ethanol for 3 weeks and for 2 weeks in the abstinence. RESULTS: After 6 weeks of topiramate and ethanol administration, the drug decreased ethanol-induced changes in the midbrain reticular formation, hippocampus and frontal cortex. In the abstinence, the drug also inhibited the features of neuronal hyperactivity, especially in the hippocampus. Moreover, topiramate co-administered with ethanol for 3 weeks decreased ethanol-induced memory disturbance in rats. This beneficial effect was also observed in the second week of abstinence. CONCLUSION: These findings reveal that 'antialcoholic' activity of topiramate may be associated with its advantageous effect on memory and learning processes.

The possibility of adverse effect of Kv7-channel opener retigabine on memory processes in rats.

OBJECTIVE: Retigabine is a novel antiepileptic drug with a unique and complex mechanism of action which allows its use in many diseases associated with impaired neuronal activity. This study sought to examine the impact of retigabine on two types of memory in rats. METHODS: Adult male Wistar rats were used to assess the effect of retigabine, administered p.o. as single (10mg/kg or 20mg/kg) or repeated doses, on spatial memory with the Morris water maze test (MWM) and emotional memory, associated with fear, with the passive avoidance test (PA). RESULTS: Retigabine administered at a high single dose transiently impairs learning processes in rats. In the MWM, these changes were delayed in time and of a lesser degree when retigabine was given at low single dose. Additionally, the drug administered repeatedly for 2weeks slowed learning processes in the MWM, but this effect occurred only after 1week of administration in the PA. CONCLUSION: These findings indicate that retigabine may affect memory and learning processes, especially in the first phase of administration.

The Impact of Zonisamide on the Development and Course of Alcohol Dependence in Rabbits. A pharmaco-EEG study.

AIMS: Zonisamide is a new anti-epileptic drug whose mechanism of action is associated with neurotransmission systems also involved in the pathogenesis of addiction. Recently, the role of memory processes and the hippocampus (Hp) is underlined in dependence. In our previous study, we determined that zonisamide decreases changes in hippocampal bioelectric activity induced by a single dose of ethanol. METHODS: This study uses a pharmaco-EEG method to examine the impact of zonisamide on the development and course of alcohol dependence in rabbits. Quantitative changes in EEG were observed in the midbrain reticular formation, Hp and frontal cortex. Zonisamide was administered p.o. once a day at dose of 30 mg/kg/day during the entire experiment. Solutions with increasing concentrations of ethanol were administered for 6 weeks, followed by a 2-week period of abstinence. RESULTS: The long-term administration of ethanol caused characteristic changes in rabbit EEG recordings, which were associated with a shift toward lower frequencies resulting in a depressive effect on the bioelectric activity of selected brain structures. Co-administration of zonisamide and ethanol caused a reduction of ethanol-induced alterations. Changes in EEG recordings were different during period of abstinence and were associated with potent shift toward the high frequencies. Zonisamide significantly decreased encephalographic features of neuronal hyperactivity when administered during the abstinence. CONCLUSION: Zonisamide decreases ethanol- and abstinence-induced changes in the EEG recordings. These effects may be a significant part of drug's mechanism of action in alcohol addiction therapy. SHORT SUMMARY: A pharmaco-EEG method was used to determine the influence of a new anti-epileptic drug zonisamide on the development and course of alcohol dependence in rabbits. The drug co-administered with ethanol decreased alcohol-induced changes in selected brain structures. Zonisamide also decreases abstinence-induced changes in the EEG recordings.

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

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.

Beneficial effect of retigabine on memory in rats receiving ethanol.

BACKGROUND: Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. METHODS: Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. RESULTS: The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. CONCLUSIONS: This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug's impact on the development of addiction.