Gamma-decanolactone attenuates acute and chronic seizures in mice: a possible role of adenosine A1 receptors
| Autor: | Gabriela Gregory Regner, José Angel Fontenla, Débora Aguirre Gonçalves, Patrícia Pereira, Pricila Pflüger, Jordana Griebler Luft, Chris Krebs |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.drug_class Adenosine A2A receptor Pharmacology 03 medical and health sciences Adenosine A1 receptor Lactones Mice 0302 clinical medicine Receptors GABA Seizures medicine Animals business.industry GABAA receptor Receptor Adenosine A1 Bicuculline Receptor antagonist Adenosine Adenosine receptor 030227 psychiatry Psychiatry and Mental health Disease Models Animal Neuroprotective Agents Acute Disease Chronic Disease Kindling model business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Behavioural pharmacology. 31(6) |
| ISSN: | 1473-5849 |
| Popis: | This study aimed to investigate the possible gamma-decanolactone mechanisms of action in the GABAergic and adenosine systems using the aminophylline-induced acute crisis model and the pentylenetetrazole-induced kindling model. In the acute model, male mice received administration of bicuculline (GABAA receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (A1 receptor antagonist) or ZM241385 (A2A receptor antagonist), 15 min before the treatment with gamma-decanolactone (300 mg/kg). After a single dose of aminophylline was administered, the animals were observed for 60 min. In the chronic model of seizure, 30 min after the treatment with gamma-decanolactone, mice received pentylenetetrazole once every third day. On the last day of kindling, the animals received the same GABA and adenosine antagonists used in the acute model, 15 min before gamma-decanolactone administration. The protein expression of GABAA α1 receptor and adenosine A1 receptor was detected using western blotting technique in hippocampal samples. The results showed that gamma-decanolactone increased the latency to first seizure and decreased seizure occurrence in the acute and chronic models. The adenosine A2A receptor antagonist and GABAA receptor antagonist were not able to change gamma-decanolactone behavioral seizure induced by aminophylline or pentylenetetrazole. The administration of adenosine A1 receptor antagonist reversed the protective effect of gamma-decanolactone in both models. In addition, gamma-decanolactone promoted an increase in the expression GABAA α1 receptor, in the hippocampus. The results suggest that the neuroprotective effect of gamma-decanolactone observed during the investigation could have a straight connection to its action on A1 adenosine receptors. |
| Databáze: | OpenAIRE |
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