EXPERIMENTAL RESEARCH SHOWING THE BENEFICIAL EFFECT
OF ORAL ZINC ADMINISTRATION IN OPIOID TOLERANCE
DIANA CIUBOTARIU1, CRISTINA MIHAELA GHICIUC1, RAOUL VASILE LUPUȘORU2*,
NELA BIBIRE3, LUMINIŢA AGOROAEI4, CĂTĂLINA ELENA LUPUȘORU1
“Grigore T. Popa” University of Medicine and Pharmacy, 16 Universităţii Street, code 700115, Iaşi, Romania
1Faculty of Medicine, Department of Pharmacology
2Faculty of Medicine, Department of Pathophysiology
3Faculty of Pharmacy, Department of Analytical Chemistry
4Faculty of Pharmacy, Department of Toxicology
*corresponding author: rvlupusoru@yahoo.com
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Abstract:
There are studies showing that zinc attenuates opioid-dependence. The aim of the present study was to assess the effect of
oral zinc sulphate on opioid analgesia in tolerant rats. Analgesia was assessed in 3 rat groups: non-dependent (group A) and
dependent (groups B and C), each with 3 subgroups. Dependence was induced with morphine in increasing doses (B: 5-day
schedule, C: 10-day schedule; from 5 mg/kg bw - day 1 to 40 mg/kg bw - day 5, respectively 90 mg/kg bw - day 10).
Subgroups 1 received saline, subgroups 2 and 3 received ZnSO4, 14 days, 2 mg, respectively 4 mg/kg bw/day, orally, before
inducing dependence in groups B and C. Basal and exposure latencies were assessed by the tail-flick test, before and 30 min
after morphine administration: 5 mg/kg bw (group A, at the end of zinc treatment); 10 mg and 15 mg/kg bw (groups B and C,
at the end of dependence schedule). Morphine induced strong analgesia in naïve and tolerant rats. In subgroup 1, the exposure
latency increased vs. basal with 41% in group A (from 10.2 ± 0.4 s to 14.5 ± 0.4 s; p < 0.001) and with 19%, respectively
15% in groups B and C, where analgesia was reduced vs. non-dependent rats. Zinc did not influence pain perception. Zinc
supplementation in patients on opioids for pain is worth being evaluated.

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