Chronic benzodiazepine treatment decreases postsynaptic GABA sensitivity

摘要: Benzodiazepines exert most of their pharmacological effects by a selective facilitation the postsynaptic actions GABA. Clinical, behavioural and electrophysiological studies have shown reduced drug response following chronic benzodiazepine administration. We present here evidence for decreased sensitivity to GABA administration as measured direct iontophoretic application serotonin onto serotonergic cells in midbrain dorsal raphe nucleus (DRN), known receive GABAergic input. The subsensitivity was found be dose dependent seen when diazepam three weeks or longer. Further, acute injection specific antagonist, Ro15-1788, reverse rapidly decrease observed chronically diazepam-treated animals without altering vehicle-treated rats. Decreased benzodiazepines does not appear consistently related alterations number affinity receptors benzodiazepines. Our radioligand-binding showed ability enhance binding cerebral cortical membranes from significant changes site density affinity.