Naloxone blocks morphine enhancement of kainic acid neurotoxicity

Kainic acid (KA) is a potent convulsant which, when administered subcutaneously, induces sustained limbic seizures and a pattern of limbic brain damage that is thought to be seizure-mediated. Diazepam suppresses and morphine enhances both the seizures and brain damage induced by KA. Here we show that morphine enhancement of KA neurotoxicity is blocked in a dose-dependent manner by subcutaneous pretreatment with naloxone. Theses and related findings support the hypothesis that morphine enhances the seizure-linked neurotoxicity of KA by an opiate specific action at certain limbic receptor sites where opiates suppress GABAergic activity, thereby lowering the threshold for propagation of seizure activity in limbic circuits.