Abstract:

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 by naloxone. 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.

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