Aim: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioid
dependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and gamma aminobutyric acid
(GABA), as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, an
antiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotor
activity during naloxone-induced withdrawal in morphine-dependent rats.
Materials and Methods: Twenty male Sprague-Dawley rats were divided in topiramate treatment and control groups. All animals
received morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On the
last day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggered
Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-induced
morphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of the
withdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not change
locomotor activity behavior such as vertical and ambulatory activity, and total covered distance.
Conclusion: These findings show that local microinjection of topiramate into the nucleus accumbens is effective in preventing opioid
deprivation symptoms without significant effect on locomotor activity.
Keywords: Morphine, nucleus accumbens, withdrawal, topiramate