The effect of NMDA receptor antagonists on the development of sensitization to diazepan withdrawal signs in mice

• Autorzy: Talarek S. , Listos J. , Orzelska J. , Lupina M. , Fidecka S.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Repeated administration of benzodiazepines can alter GABAA receptors, which contributes to the development of dependence and often limits their clinical use. Although multiple chemical mediators are now hypothesized to be involved in the addictive effect of benzodiazepines, the mechanisms involved in the benzodiazepine dependence are not fully understood. The aim of the present study was to investigate the effects of two uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine and memantine, on the development of sensitization to diazepam withdrawal signs in mice. METHODS: In order to show the sensitization to benzodiazepine withdrawal signs the animals were divided into groups: the animals continuously (for 21 days) treated with diazepam (15 mg/kg/day sc) and the animals receiving diazepam during three 7-day periods interspersed with 3 day diazepam-free period in which the animals were treated with vehicle injections. Ketamine (2.5, 5 mg/kg ip) or memantine (2.5, 5 mg/kg ip) were administrated in sporadic diazepam treated mice during the diazepam-free periods (three, daily injections in each of the periods). In all animals, the intensity of diazepam withdrawal signs, observed as the increase in seizure activity (in pentylenetetrazole (PTZ)-induced seizures model) was assessed 48 h after the last injection of diazepam or vehicle. The animals, after concomitant administration of subthreshold dose of PTZ (55 mg/kg sc) with flumazenil (5 mg/kg ip), were placed in glass cylinders and were observed for 60 min. RESULTS: The present experiments showed that administration of ketamine (2.5, 5 mg/kg) or memantine (2.5, 5 mg/kg) during two diazepam drug-free periods in sensitized mice, significantly attenuated their seizures activity. CONCLUSION: These findings support the hypothesis that glutamatergic system is involved in the mechanisms of sensitization to withdrawal signs precipitated after sporadic treatment with diazepam.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S80

Twórcy

autor

Talarek S.

• Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland

autor

Listos J.

• Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland

autor

Orzelska J.

• Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland

autor

Lupina M.

• Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland

autor

Fidecka S.

• Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland