Ro 15-1788 suppresses the development of kindling through the benzodiazepine receptor
Abstract:
beta-Carboline (norharman) has been shown to produce kindled seizures when given systemically for long periods of time. The expression of the kindled seizure activity can be blocked by ligands of the benzodiazepine receptor suggesting the receptor as a site of vulnerability in the kindling mechanism. The present data show that Ro 15-1788, a receptor antagonist, suppresses the development of kindled seizures as demonstrated by the delayed appearance of each behavioral stage and the decreased severity of symptoms within each stage. Animals treated with Ro 15-1788 still expressed lower behavioral stages when Ro 15-1788 was eliminated from the trials indicating that this compound suppresses the very process of kindling itself and not just the expression of the kindled seizures. Ro 15-1788 given with norharman causes an increase in Bmax of [3H]flunitrazepam binding to the benzodiazepine receptor in cortex. It is not known if this increase is instrumental in lowering the kindling rate.
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