Diazepam dependence prevented by glutamate antagonists

摘要: Long-term treatment leads to tolerance and dependence on benzodiazepines. Abrupt termination of benzodiazepine administration triggers the expression signs dependence. Mice withdrawn from chronic with diazepam showed a time-related evolution anxiety, muscle rigidity, seizures between days 4 21 after discontinuation. A period withdrawal 1 3 was symptom-free. Surprisingly, during this "silent phase" susceptibility mice alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate (ATPA) kainate magnitude monosynaptic reflexes mediated by non-N-methyl-D-aspartate (NMDA) mechanisms were enhanced. In apparent contrast, "active phase", 21, characterized increased NMDA enhanced polysynaptic reflexes, which are dependent. Treatment alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) or 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline but not antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) silent phase prevented CPP GYKI 52466 active symptoms. The development concurrent 52466. These data indicate that NMDA-dependent contribute in long-term diazepam. Nevertheless, non-NMDA-mediated is essential for triggering Therefore, AMPA may offer therapeutic approach preventing benzodiazepines an alternative antagonism.