RESUMO
Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.
Assuntos
Analgésicos Opioides/administração & dosagem , Anticonvulsivantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões/prevenção & controle , Tramadol/administração & dosagem , Analgésicos Opioides/toxicidade , Animais , Anticonvulsivantes/toxicidade , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Ratos Wistar , Receptores de AMPA/genética , Receptores de N-Metil-D-Aspartato/genética , Convulsões/induzido quimicamente , Convulsões/metabolismo , Convulsões/fisiopatologia , Índice de Gravidade de Doença , Tramadol/toxicidade , CalponinasRESUMO
The goal of this article is to clarify the role of various growth factors in the establishment and progression of obsessive-compulsive disorder (OCD). OCD is a chronic mental disorder with recurrent intrusive thoughts and/or repetitive compulsive behaviors that increase during stressful periods. Growth and neurotrophic factors may be contributing factors in the pathophysiology of OCD. Many of them are synthesized and released within the central nervous system and act as trophic agents in neurons; some of them are involved in brain growth, development, neurogenesis, myelination and plasticity, while others take part in the protection of the nervous system following brain injuries. This paper attempts to identify all articles investigating the relationship between OCD and neurotrophic and growth factors, in both animal and human studies, with a focus on adult brain studies. Based on the PubMed and Scopus and Science Direct search tools, the available articles and studies are reviewed. Out of 230 records in total, the ones related to our review topic were taken into account to further understand the pathophysiological mechanism(s) of OCD, providing methods to improve its symptoms via the modification of neurotrophins and growth factor imbalances.
