Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae

Abstract

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)