ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
capítulos de libros
Título:
Effect of chronic benzodiazepine Exposure on GABAA receptors: Regulation of GABA/benzodiazepine site interactions
Autor/es:
MARIA CLARA GRAVIELLE
Libro:
Neuropathology of Drug Addictions ans Substance Misuse
Editorial:
Elsevier
Referencias:
Año: 2016; p. 308 - 316
Resumen:
Chronic benzodiazepine consumption has been limited by the development of toleranceto most of the pharmacological effects of these drugs and dependence. Because GABAA receptors mediate most of the pharmacological effects of benzodiazepines, they play an important role in the adaptive mechanism responsible for tolerance and dependence induced by prolonged benzodiazepine administration. This chapter focuses on the alterations inthe GABAA receptor structure and function that are associated with the development of tolerance and dependence produced by chronic benzodiazepine exposure. Chronic benzodiazepine administration induces selective changes in the levels of different GABAA receptor subunits,whichmay lead to alterations in the receptor subunit composition. These changes vary depending on the treatment protocol and the brain region analyzed. Tolerance is also associated with a decrease in allosteric coupling between GABA and benzodiazepine sites. However, the relevance of uncoupling to the tolerance observed in vivo remains to be determined.