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Effect of Linalool on Morphine Tolerance and Dependence in Mice
Author(s) -
Hosseinzadeh Hossein,
Imenshahidi Mohsen,
Hosseini Mohammadreza,
Razavi Bibi Marjan
Publication year - 2012
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3736
Subject(s) - morphine , linalool , pharmacology , nmda receptor , chemistry , (+) naloxone , agonist , opioid , antagonist , memantine , receptor , medicine , biochemistry , chromatography , essential oil
Linalool, a terpene alcohol, has been shown to interact with the opioid system and N ‐methyl‐ d ‐aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and100 mg/kg), clonidine (positive control), alpha‐2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail‐flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. Copyright © 2012 John Wiley & Sons, Ltd.