Epilepsy Res., 10 (1991) 103-110 103 Elsevier EPIRES 00434 Effects of chronic naloxone pretreatment on amygdaloid kindling in rats Luisa Rocha 1'4'5, Jerome Engel Jr. 1,2,3 and Robert F. Ackermann 1'3 Departments of]Neurology and 2Anatomy and Cell Biology, SBrain Research Institute, UCLA, Los Angeles, CA (U.S.A.), 41nstituto Mexicano de Psiquiatria and SDepartamento de Farmacologia, Fac. de Medicina, UNAM (Mexico) (Received 15 February 1991; revision received 15 July 1991; accepted 2 August 1991) Key words: Amygdala; Kindling; Naloxone; Opioid receptors; Upregulation Effects of chronic naloxone pretreatment (75 or 270/~gha for 14 days) on the development of amygdaloid kindling in rats were evalu- ated. The acquisition of seizure activity was modified in the naloxone pretreated animals, depending on the nucleus stimulated: facili- tation of stages IV and V occurred in 37%, variability of electrographic and behavioral responses to electrical stimulation during the kindling development in 33%, and facilitation of stages IV and V followed by long periods of seizure suppression in 29%. Enhance- ment of postictal seizure suppession during a recycling paradigm was observed in all the naloxone pretreated rats. It was concluded that the chronic administration of naloxone (known to induce opioid binding upregulation and supersensitivity),in association with the enduring changes in opioid mechanisms provoked by kindled seizures, were responsible for the facilitation and suppression of epilep- tic activity. These findings support bidirectional modulatory effects of opioid peptides on epileptic seizures as well as the view that epi- leptic seizures can induce enduring alterations in opioid mechanisms. INTRODUCTION It is known that opioid peptides play an impor- tant role in seizure mechanisms. The brain content of these peptides is modified following acute and chronic experimental seizures in animals zT' 28,33-35,39,46-48, as well as in cerebrospinal fluid of patients with epilepsy 29. Previous studies have shown effects of opiates on postictal and interictal behaviors. Specifically, administration of morphine increases the duration of postictal depression in amygdaloid kindled Correspondence to: Luisa Rocha, M.D., UCLA Neurology Department, Reed Neurological Research Center, 710 West- wood Plaza, Los Angeles, CA 90024, U.S.A. rats21, whereas naltrexone and naloxone reduce the duration of this phenomenon in hippocampus- or amygdala-kindled rats9'21'45. It is believed that the activation of endogenous opioid systems by electroconvulsive seizures inhibits kindling in rats3s'44, and that the release of opioid peptides by kindled seizures provokes postictal motor deficits, postictal explosive behavior and seizure suppres- sion, which are mediated by the activation of opi- oid receptors in a heterogeneous manner3-7. In rats, repeated daily electroconvulsive shock (ECS) treatment increases opioid receptor bind- ing, an event that parallels the regional increases in brain enkephalin following ECS 25'26. Opiate re- ceptor binding is reported to be greater (upregula- tion) in the epileptogenic temporal lobe of patients 0920-1211/91/$03.50 © 1991 Elsevier Science Publishers B.V. All rights reserved