THE INFLUENCE OF MONTELUKAST ON MORPHINE-INDUCED
PHYSICAL DEPENDENCE
MIHAI NECHIFOR*, MAGDALENA CUCIUREANU, DAN CHELĂRESCU, DIANA CIUBOTARIU
Department of Pharmacology, “Gr. T. Popa” University of Medicine and Pharmacy, 16 Universitatii Street, 700115, Iasi,
Romania
*corresponding author: mnechifor@yahoo.com
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Abstract:
This study investigates the influence of montelukast (MK), a cysteinyl-leukotriene 1 (CysLT1) receptor antagonist, on
morphine-induced physical dependence in rats. The study was carried out on four groups of 10 Wistar male rats each, as
follows: group I (control) - saline, s.c.; group II - MK 10 mg/kg b.w. p.o./day for 10 days; group III - morphine s.c.
(progressively increasing doses from 5 mg/kg b.w./day in 1st day to 90 mg/kg b.w. day in 10th day) and group IV - MK 10
mg/kg b.w. p.o. and morphine s.c. (as group III) 10 days. On the 11th day, the morphine and MK administration was stopped
and all animals received naloxone i.p. 2 mg/kg b.w. and withdrawal syndrome was assessed for 30 minutes. MK association
to morphine (group IV) significantly reduced the intensity of morphine-induced physical dependence and the withdrawal
symptoms such as: grooming (8.3 ± 3.52 in morphine + MK group versus 12.4 ± 2.87 in morphine only, p < 0.01),
compulsive mastication (10 ± 1.82 versus 12.7 ± 2.75, p < 0.05), palpebral ptosis (2.1 ± 0.87 versus 3.5 ± 0.97, p < 0.01), and
decreased Gellert Holtzman score (88.5 ± 15 in morphine + MK group versus 119.3 ± 17.8 in morphine only group p < 0.01.
The data show that cysteinyl-leukotrienes (CysLTs) are involved in morphine-induced dependence and that the MK
administration during induction of morphine dependence, but not during withdrawal, alleviates the intensity of the
withdrawal syndrome symptoms in rats.

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