PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Sleep-Wake Stage-Dependent qEEG Effects of Acute Tramadol Suggest a Potential Antidepressant Effect

Text of the abstract

Introduction: Tramadol hydrochloride (TRA) is a widely prescribed opioid analgesic with additional inhibitory effects on the synaptic reuptake of serotonin (5-HT) and noradrenaline. Its potential use as an antidepressant in the treatment of major depression has been suggested. Most antidepressants show characteristic effects on quantitative electroencephalographic (qEEG) variables. For instance, we showed that chronic escitalopram treatment elicited an increase in gamma power during non-REM sleep. Similarly, acute administration of an 5-HT2C-R antagonist (SB-242084) with fast-onset antidepressant-like properties also elevated gamma power during non-REM sleep.
Aims: Our aim was to investigate the acute effects of tramadol on qEEG in different sleep-wake stages.
Methods: EEG-equipped male Wistar rats were treated with TRA (5, 15 and 45 mg/kg i.p.) or vehicle (VEH) at the beginning of the passive phase, and EEG, electromyogram (EMG) and motor activity (MOT) were recorded.
Results: QEEG analysis revealed that delta power during non-REM sleep was markedly increased by the two higher doses of TRA, 5 h after administration. However, the 15 mg/kg of TRA decreased delta power in the first hours. Delta power during wakefulness was also increased by TRA (15 and 45 mg/kg), 3 h after administration. Alpha power was decreased by TRA (15 and 45 mg/kg) during NREM sleep, while during wakefulness TRA showed no effect. All doses of TRA increased gamma power during NREM sleep. In contrast, TRA slightly reduced gamma power during wakefulness.
Conclusion: Our findings provide evidence that acute TRA affects qEEG in a sleep-wake stage-dependent manner. Some of these effects of TRA are similar to those observed in case of the chronic administration of 5-HT reuptake inhibitors or the acute effects of fast acting antidepressants. Therefore, qEEG effects of TRA suggest antidepressant-like properties, moreover, raise the possibility of faster acting antidepressant action.

Funding: This study was supported by the Development of Scientific Workshops of Medical, Health Sciences and Pharmaceutical Educations (EFOP-3.6.3-VEKOP-16-2017-00009).