Intraamygdaloid morphine produces seizures and brain damage in rats.

Behavioral and neuropathological responses to increasing doses of morphine hydrochloride (10-75 micrograms) administered into the rat amygdala were studied. Unilateral microinjections of morphine in doses of 40 and 75 micrograms produced a sequence of behavioral alterations including staring spells, gustatory automatisms, wet dog shakes, motor limbic seizures and limbic status epilepticus. Lower doses of morphine (10 and 20 micrograms) showed different threshold for these behavioral phenomena but a similar time course of development. Histological examination of frontal forebrain sections revealed widespread, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, thalamus, neocortex, hippocampal formation and amygdaloid complex. Pretreatment of animals with diazepam (10 mg/kg i.p.) prevented the development of sustained limbic seizures and brain damage caused by morphine, while pretreatment with naloxone hydrochloride (2-20 mg/kg i.p.) failed to affect morphine-induced convulsant activity and brain damage. These results may suggest that morphine elaborates sustained limbic seizures and widespread brain damage by mechanism underlying the antagonism of inhibitory amino acid neurotransmission and opioid receptors do not seem to be involved.