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

Krupa-Burtnik, Agata; Zwierzyńska, Ewa; Kordala, Anna; Pietrzak, Bogusława

doi:10.1093/alcalc/agx003

Cited by 3 publications

(3 citation statements)

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“…Being a drug with a multidirectional mechanism of action, zonisamide could modulate the activity of the hippocampus and neurotransmitter pathways involved in memory processes. Our previous pharmaco-electroencephalography study found that zonisamide decreased alcohol-and abstinence-induced changes in selected brain structures involving the hippocampus [17]. Hence, the aim of the present study was to assess the effect of zonisamide on memory processes during prolonged exposure to ethanol and also after its discontinuation.…”

Section: Introductionmentioning

confidence: 91%

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

Pietrzak

Krupa-Burtnik

Zwierzyńska

2023

IJERPH

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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.

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Section: Introductionmentioning

confidence: 91%

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

Pietrzak

Krupa-Burtnik

Zwierzyńska

2023

IJERPH

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“…Also acts via inhibition of 'T' type calcium current. It also alters the concentration of γ-glutamyl-transferase which is a measure of alcohol consumption [97] Open-label study as per DSM-IV demonstrated that, zonisamide treatment cause significant improvement in the visual analogue scale for craving severity scores and weekly drink consumption in 22 outpatients [98] Muscles fatigue, somnolence, dizziness and ataxia [98] Pregabalin (Maximum 450 mg/day) Newer congener of gabapentin Pregabalin is selectively binds to the α2 subunit of voltagegated calcium channels and inhibits the release of excitatory neurotransmitters [99] In the open-label trial, treatment with pregbalin caused a significant progressive reduction of both craving and withdrawal symptomatology in 20 patients compared to placebo [100] Rashes, allergic reactions Baclofen (30-180 mg/day) Centrally acting muscle relaxant, reduces the acquisition of alcoholdrinking behaviour A selective GABA B receptor agonist, voltage-gated N-type calcium channel blocker and also acts as a suppressor of alcohol-stimulated dopamine release in the mesolimbic dopamine system probable mechanism in the treatment of AUD [101] In preclinical studies treatment with baclofen showed dose-dependent reduction in the self-administered alcohol in rats under operant self-administration conditions [102] Drowsiness, weakness, dizziness, tiredness, trouble sleeping, headache nausea, constipation, increased urination [102] Ondansetron (4 μg twice daily)…”

Section: Vareniclinementioning

confidence: 99%

Neurochemical Evidence of Preclinical and Clinical Reports on Target-Based Therapy in Alcohol Used Disorder

et al. 2020

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Alcohol use disorder (AUD) is a chronic relapsing disorder, which enforces a person to compulsively seek alcohol, restricting control over alcohol intake leads to emergence of an undesired emotional state during abstinence. There are recent advances for better understanding of neurocircuitry involved in the pathophysiology of AUD. Alcohol interaction with neuronal membrane proteins results in changes in neuronal circuits. It is also linked with the potential medication and their clinical validation concerning their pharmacological targets for alcoholic abstinence. This review covers research work from the past few decades on the therapeutic advances on treatment of alcohol dependence; further detailing the fundamental neurochemical mechanisms after alcohol administration. It also covers interaction of alcohol with GABAergic, glutaminergic, dopaminergic, serotonergic and opioid systems. This review further elaborated the neurobiology of noradrenergic, cholinergic and cannabinoid systems and their interaction with AUD. Elaborative information of potential drug targets under current exploration for AUD treatment with their mechanisms are reported here along with clinical outcomes and the associated side effects.

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“…A clinical study indicated that zonisamide reduced the stimulatory impacts of AA in patients [22]. Previous studies have used various dosages of zonisamide across different species (rabbits at 3-30 mg/kg [23,24], mice at 0, 25, 50 mg/kg [25], and rats at 25-50 mg/kg [25,26]), indicating its effectiveness against neurological complications. Kumar et al [27] studied a higher dose of zonisamide (100 mg/kg) in rats and demonstrated significant neuroprotective potential against seizures by mitigating oxidative stress, inflammation, and neuronal death, indicating its promise as a neuroprotective agent for epilepsy and other neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Zonisamide Ameliorated the Apoptosis and Inflammation in Cerebellar Tissue of Induced Alcohol Addiction Animal Model

Aşır,

Erdemci,

Çankırı

et al. 2024

Life

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This study investigated the effects of zonisamide treatment on cerebellar tissues in an experimental alcohol addiction (AA) model and its potential mechanisms of action, particularly regarding apoptotic protease activating factor-1 (APAF-1) and tumor necrosis factor-alpha (TNF-α) expression. Thirty rats were divided into three groups: sham, ethanol (EtOH), and EtOH + zonisamide. AA was induced by administering 6 cc of EtOH orally every 8 h for 4 days. Zonisamide (100 mg/kg) was given to rats once daily before EtOH administration. Motor defects were evaluated using an open field maze. Serum TNF-α levels were measured from blood samples. Cerebellar sections were processed for histological examination and immunostained for APAF-1 and TNF-α. Protein interaction networks were constructed using Cytoscape, and functional annotations were performed with ShinyGO (version 0.80) software. The traveled area in the EtOH group was significantly reduced compared to the sham group (p = 0.0005). Rats in the EtOH + zonisamide group covered a larger area, with zonisamide treatment significantly improving locomotor ability compared to the EtOH group (p = 0.0463). Serum TNF-α levels were significantly elevated in the EtOH group compared to the sham group (p < 0.0001) and were significantly decreased in the EtOH + zonisamide group compared to the EtOH group (p = 0.0309). Regular cerebellar histological layers were observed in the sham group, while EtOH induction caused loss of cerebellar tissue integrity, neuronal degeneration, vascular dilatation and congestion, reduced myelin density, and neuropils in the EtOH group. Zonisamide treatment improved these pathologies, enhancing myelination and neuropil formation. Negative APAF-1 and TNF-α expressions were observed across cerebellar layers in the sham group. Due to EtOH toxicity, APAF-1 and TNF-α expression were upregulated in the EtOH group compared to the sham group (p < 0.001 for both). Zonisamide treatment downregulated these protein expressions in the EtOH + zonisamide group compared to the EtOH group (p < 0.001 and p = 0.0087, respectively). APAF-1 was primarily associated with AA through antifolate resistance, endopeptidases, and the interleukin-1 pathway, while TNF-α was predominantly enriched in infections and choline-binding, indicating zonisamide’s impact on immune and inflammatory pathways. In conclusion, zonisamide treatment significantly mitigated ethanol-induced cerebellar damage and inflammation in an AA model. Zonisamide improved locomotor function and reduced serum TNF-α levels, as well as APAF-1 and TNF-α expression in cerebellar tissues. These findings suggest that zonisamide exerts its protective effects by modulating immune and inflammatory pathways, thereby preserving cerebellar integrity and function.

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

Cited by 3 publications

References 28 publications

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

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

Neurochemical Evidence of Preclinical and Clinical Reports on Target-Based Therapy in Alcohol Used Disorder

Zonisamide Ameliorated the Apoptosis and Inflammation in Cerebellar Tissue of Induced Alcohol Addiction Animal Model

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