The threshold for limbic seizures in rats is decreased by intranigral morphine.

Microinjection of morphine hydrochloride into the substantia nigra pars reticulata, bilaterally, converts non-convulsant dose of pilocarpine hydrochloride, 100 mg/kg, into a convulsant one. The ED50 of morphine for the generation of seizures after pilocarpine, 100 mg/kg, is 3.8 nmol (2.5-5.8). Electrographic and behavioral monitoring both show a pattern of convulsant activity similar to those produced by pilocarpine in doses exceeding 350 mg/kg. Morphological analysis of frontal forebrain sections reveals epilepsy-related damage to the hippocampus, thalamus, olfactory cortex, substantia nigra, neocortex and amygdala. The proconvulsant action of morphine in the substantia nigra is reversed by co-administration of naloxone hydrochloride. The results show that the threshold for limbic seizures may be modulated by opiates in the substantia nigra.