Evidence for the Involvement of the Dopaminergic System in Seizure and Oxidative Damage Induced by Tramadol

• Published in: International journal of toxicology Vol. 37; no. 2; p. 164
• Main Authors: Bameri, Behnaz, Shaki, Fatemeh, Ahangar, Nematollah, Ataee, Ramin, Samadi, Mahedeh, Mohammadi, Hamidreza
• Format: Journal Article
• Language: English
• Published: United States 01.03.2018
• Subjects: Analgesics, Opioid - adverse effects; Animals; Brain - drug effects; Brain - metabolism; Cabergoline - pharmacology; Dopamine Agonists - pharmacology; Dopamine D2 Receptor Antagonists - pharmacology; Glutathione - metabolism; Haloperidol - pharmacology; Male; Malondialdehyde - metabolism; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Oxidative Stress; Protein Carbonylation; Reactive Oxygen Species - metabolism; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Seizures - chemically induced; Seizures - metabolism; Tramadol - adverse effects; tramadol; seizure; dopaminergic; mitochondria; oxidative stress
• ISSN: 1092-874X
• DOI: 10.1177/1091581817753607

Tramadol (TR) is a synthetic analgesic drug with central function that can induce seizures even at therapeutic doses. The exact mechanism of TR effect on seizure generation is not clear, but inhibition of the serotonin and nitric oxide pathways and inhibitory effects on GABA receptors are the most common hypotheses about the seizure-inducing mechanism of the TR. This study aimed to evaluate the role of dopaminergic system on the seizure and oxidative damage induced by TR using agonist and antagonist drugs of this system in the Albino mice. Clonic seizure induced by TR was evaluated as seizure threshold. Haloperidol (0.2 mg/kg, IP), a predominantly D receptor antagonist, and cabergolin (0.5 mg/kg, IP), a dopamine agonist specific for the D receptors, were injected 60 minutes before the seizure induction. The seizure threshold was significantly increased by dopaminergic antagonist, but it was decreased significantly by pretreatment with the selective agonist. Oxidative stress biomarkers (reactive oxygen species, lipid peroxidation, and protein carbonyl content) significantly increased and glutathione content significantly decreased in brain mitochondria by TR compared with the control group, whereas oxidative markers were decreased significantly after pretreatment with haloperidol compared with the TR group. This study revealed that the dopaminergic system is involved in TR-induced seizure, and meanwhile, inhibition of dopamine D receptors can increase the TR threshold seizure and decrease the oxidative damage in the brain mitochondria. Conversely, stimulation of dopamine D receptors by cabergolin can decrease the TR threshold seizure and glutathione content in the brain mitochondria.