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Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats

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Abstract

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4 mg/kg/day, 14 days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5 mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5 mg/kg naloxone was reduced with 15%—the lower zinc dose and with 24%—the higher zinc dose; the aversion induced by 2.5 mg/kg naloxone was reduced with 16%—the lower zinc dose and with 29%—the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Pharmacology, University of Medicine and Pharmacy “Grigore T. Popa”, School of Medicine, 16 Universităţii Street, 700115, Iaşi, Romania

    Diana Ciubotariu, Liliana Mititelu-Tarțău & Cătălina Elena Lupușoru

  2. Faculty of Medicine, Department of Pathophysiology, University of Medicine and Pharmacy “Grigore T. Popa”, School of Medicine, 16 Universităţii Street, 700115, Iaşi, Romania

    Raoul Vasile Lupușoru

  3. Faculty of Dental Medicine Faculty, Fixed Prosthetics, Gnatology, Dental-Stomato-Facial Aesthetics Department, University of Medicine and Pharmacy “Grigore T. Popa”, School of Medicine, 16 Universităţii Street, 700115, Iaşi, Romania

    Elena Luca

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  1. Diana Ciubotariu
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  2. Raoul Vasile Lupușoru
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  3. Elena Luca
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  4. Liliana Mititelu-Tarțău
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  5. Cătălina Elena Lupușoru
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Correspondence to Diana Ciubotariu.

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The study protocols were approved by the institution’s Ethics Committee of Research (“Gr. T. Popa” University of Medicine and Pharmacy from Iași, Romania). All animal procedures were performed in accordance with the European Union law on the care and use of animals for scientific purposes and with the Helsinki Declaration recommendations.

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The authors declare that they have no conflict of interest.

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Ciubotariu, D., Lupușoru, R.V., Luca, E. et al. Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats. Biol Trace Elem Res 180, 127–134 (2017). https://doi.org/10.1007/s12011-017-0995-1

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  • DOI: https://doi.org/10.1007/s12011-017-0995-1

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