# The role of GABAergic receptors in acute, subacute, and withdrawal syndrome on pain and seizure thresholds in mice: A connection to mitochondrial function and oxidative stress in the brain

## TL;DR

This study shows that baclofen, a GABA receptor agonist, increases seizure thresholds and reduces oxidative damage in mice brains, especially with long-term use.

## Contribution

The study reveals the dose- and time-dependent effects of baclofen on seizure thresholds and mitochondrial oxidative stress in mice.

## Key findings

- Baclofen increased seizure thresholds in both short- and long-term exposure.
- Long-term baclofen improved mitochondrial oxidative damage by reducing ROS and MDA levels.
- Baclofen increased pain thresholds through a muscle relaxant effect.

## Abstract

One of the most serious neurological disorders is epilepsy. This study aimed to investigate the effects of baclofen, a GABA receptor agonist, on pain and seizure thresholds, as well as on oxidative damage in brain mitochondrial membranes of mice. Sixty male mice were divided into 10 groups. Control, baclofen (1, 5, and 10 mg/kg) with short-term exposure (1 day), long-term exposure (7 days), and withdrawal syndrome (eight days). The withdrawal syndrome was evaluated one day after the last dose of the drug. Hotplate and tail-flick tests were performed to assess pain threshold, and the rotarod was used to assess motor coordination. The seizure threshold and oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH), and the MTT assay, were investigated. The results showed that baclofen (10 mg/kg) in short-term and all doses (1, 5, and 10 mg/kg) in long-term increased the seizure threshold. Evaluation of motor function and coordination in mice revealed decreased motor activity. The effect of baclofen on oxidative damage showed that, in long-term exposure, it improved mitochondrial ROS, malondialdehyde, and GSH levels. Protein carbonyl and MTT tests did not show a significant difference. A GABAB receptor agonist causes a dose- and time-dependent increase in the seizure threshold. Baclofen could reduce oxidative damage by decreasing ROS levels and malondialdehyde formation, and increasing GSH content.

The effects of GABAergic Receptors in Acute, Subacute, and Withdrawal Syndrome on Pain and Seizure Thresholds in Mice.

The effects of GABAergic Receptors in Acute, Subacute, and Withdrawal Syndrome on Pain and Seizure Thresholds in Mice.

•GABAB receptor agonist increase the seizure threshold via dose and time-dependent manner.•Baclofen in long-term administration, improved brain mitochondrial damage.•Baclofen increase the pain threshold via muscle relaxant effect.•Baclofen in the short term and long term increased the seizure threshold.•Baclofen reduces oxidative damage by decreasing the oxidative damage in mitochondria

GABAB receptor agonist increase the seizure threshold via dose and time-dependent manner.

Baclofen in long-term administration, improved brain mitochondrial damage.

Baclofen increase the pain threshold via muscle relaxant effect.

Baclofen in the short term and long term increased the seizure threshold.

Baclofen reduces oxidative damage by decreasing the oxidative damage in mitochondria