Protective effects of pistachio hydroalcoholic extract on morphine-induced analgesic tolerance and dependence: investigating the impact of oxidative stress

Abstract

Background and purpose: Chronic consumption of morphine (Mor) induces tolerance and dependence. This study aimed to survey the effects of pistachio extract (PX) on the induction and expression of Mor analgesic tolerance and physical dependency in mice.

Experimental approach: Animals were randomly separated into six groups (n = 7): control, DMSO, Mor (10 mg/kg), Mor + saline, Mor + PX (10 mg/kg), and Mor + PX (100 mg/kg). Mor was injected (10 mg/kg, twice a day, s.c.) for 7 days to induce tolerance. PX was administered (10 and 100 mg/kg, orally) during the examination period. On each day and 20 min after Mor administration, a tail-flick test was done to measure the analgesic response and induction of tolerance. On day 7, naloxone (5 mg/kg, s.c.) was injected into the Mor-dependent animals to evaluate dependence, and animals were monitored for 30 min for jumping. Also, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the brain tissue.

Findings/results: Our results indicated that co-administration of PX with Mor for 7 days diminished the induction of Mor tolerance. PX administration for 7 days alongside Mor reduced the frequency of withdrawal signs in naloxone-injected animals during dependence induction. Also, Mor increased the level of MDA and decreased the activities of SOD and GPx. Treatment with PX (100 mg/kg) restored all of the mentioned abnormalities.

Conclusion and implications: According to the results presented in this study, chronic administration of PX forbade the induction of Mor analgesic tolerance and dependency in mice.

Keywords: Mice; Morphine; Physical dependence; Pistachio extract; Tolerance.

Fig. 1

Effect of chronic treatment with PX on morphine tolerance induction. Data are expressed as mean ± SEM; n = 7. ^***P < 0.001 indicates significant differences compared to the control group; ^###P < 0.001 versus the Mor group. MPE, Maximum possible effect; PX, pistachio extract; Mor, morphine.

Fig. 2

Effect of acute treatment with PX on morphine tolerance expression. Data are expressed as mean ± SEM; n = 7. ^***P < 0.001 indicates significant differences compared to the control group. MPE, Maximum possible effect; PX, pistachio extract; Mor, morphine.

Fig. 3

Effect of chronic treatment with PX on morphine dependence. Data are expressed as mean ± SEM; n = 7. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001 indicate significant differences compared with the control group; ^#P < 0.05 and ^###P < 0.001 versus the Mor group. PX, Pistachio extract; Mor, morphine.

Fig. 4

Effect of acute treatment with PX on morphine dependence. Data are expressed as mean ± SEM; n = 7. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001 indicate significant differences compared with the control group. PX, Pistachio extract; Mor, morphine.

Fig. 5

Effect of treatment with PX on SOD and GPx activities and MDA level. Data are expressed as mean ± SEM; n = 7. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001 indicate significant differences compared with the control group; ^#P < 0.05 and ^##P < 0.01 versus the Mor group. PX, Pistachio extract; Mor, morphine; SOD, superoxide dismutase; GPx, glutathione peroxidase; MDA, malondialdehyde.