The effects of gabapentin and alcohol on HEK 293 cell culture

Morić, Marina (2014) The effects of gabapentin and alcohol on HEK 293 cell culture. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

The anticonvulsant drug gabapentin showed positive results in the treatment of alcoholism and its consequences. Although mechanisms of gabapentin action are not fully understood, studies suggested that gabapentin neuroprotective effects could be achieved via GABAA receptors. Treatment with ethanol at concentrations higher than 100 mM for 96 hours reduced the number of HEK 293 cells, untransfected or transfected with α1β2γ2S GABAA receptors. The cytotoxic effect of ethanol was counteracted by co-administration of 1 μM gabapentin in transfected, but not in untransfected cells. Exposure to 100 mM ethanol induced an increase in the number of binding sites for benzodiazepines and convulsants, while this effect was reversed by simultaneous exposure to 1 μM gabapentin, 100 μM bicuculline or their combination. Administration of ethanol, as well as bicuculline, induced functional allosteric uncoupling of GABA and benzodiazepine binding site, which was prevented by simultaneous gabapentin treatment. Increase in mRNA expression of α1, β2 and γ2S GABAA receptor subunits was not influenced by the exposure to ethanol or gabapentin, but only by their co-administration. Although results support the hypothesis of the involvement of GABAA receptors in the actions of gabapentin, further research is needed to elucidate the mechanisms of gabapentin protective effects against ethanol-induced cytotoxicity.

Item Type: Thesis (Diploma thesis)
Keywords: gabapentin, long-term treatment, alcohol, recombinant GABAA receptors, HEK 293 cell culture, cytotoxicity
Supervisor: Švob Štrac, Dubravka
Co-supervisor: Hranilović, Dubravka
Date: 2014
Number of Pages: 60
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 25 Nov 2014 10:08
Last Modified: 25 Nov 2014 10:08
URI: http://digre.pmf.unizg.hr/id/eprint/3361

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