Brain Serotonin Content Regulates the Manifestation of Tramadol-induced Seizures in Rats

Abstract

The authors determined that serotonin-reduced rats were predisposed to tramadol-induced seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

Parachlorophenylalanine‐induced 5‐HT depletion alters behavioral and brain neurotransmitters levels in 6‐Hz psychomotor seizure model in mice

“…The modulatory role of the brain neurotransmitters in various models of epilepsy is already reported . In our study too, we found that 6‐Hz psychomotor seizures were accompanied by reduced brain levels of 5‐HT, DA, NE, histamine and GABA, and enhanced levels of Glu.…”

Tramadol: Distinguishing the Pathophysiology of Serotonin Syndrome and Seizures

“…However, recent animal data strongly questioned their serotoninergic origin. Rat pretreatment with cyproheptadine, a serotonin receptor antagonist, did not abolish tramadol-induced seizures 4 while 5-hydroxytryptophane/benserazide, a combination enhancing brain serotonin concentration, was protective 5 or without effects on seizures. 4 These observations contrasted with the preventive effects of cyproheptadine on seizures induced by citalopram, a serotoninreuptake inhibitor, 6 suggesting that drug-related SS is a heterogeneous entity.…”

Is naloxone the best antidote to reverse tramadol-induced neuro-respiratory toxicity in overdose? An experimental investigation in the rat

“…In contrast, the exact mechanisms of tramadol-induced seizures are still poorly understood. Based on animal data, seizures are unlikely to be related to serotoninergic mechanisms [19,20] and alternative pathways including GABAergic [21], histaminergic [22], and opioidergic [21] have been hypothesized, thus questioning the possible worsening role of naloxone in the treatment of tramadol overdose. Conformingly, in one observational study, naloxone administration was associated with increased probability of tracheal intubation [11].…”