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. 2021 Jun 30;16(4):391-399.
doi: 10.4103/1735-5362.319577. eCollection 2021 Aug.

Thymoquinone abrogates methamphetamine-induced striatal neurotoxicity and hyperlocomotor activity in mice

Ali Roohbakhsh  1   2 , Mohammad Moshiri  3 , Azam Salehi Kakhki  4 , Milad Iranshahy  5 , Fatemeh Amin  6   7 , Leila Etemad  1
Affiliations

Thymoquinone abrogates methamphetamine-induced striatal neurotoxicity and hyperlocomotor activity in mice

Ali Roohbakhsh et al. Res Pharm Sci. .

Abstract

Background and purpose: Methamphetamine (METH) abuse has devastating consequences on the nervous system. There are limited therapy choices in METH abuse with reduced effectiveness and elevated recurrence rates. Thymoquinone (TQ), the most bioactive constituent of Nigella sativa seeds exerts neuroprotective effects mainly via antioxidant properties. This study aimed to evaluate the effect of TQ against METH-induced striatal neurotoxicity and hyperlocomotor activity in mice.

Experimental approach: Our groups of animals received METH (10 mg/kg) four times a day with 2 h intervals. Normal saline or TQ (5, 10, or 20 mg/kg) was injected intraperitoneally 30 min before METH administration. Control and sham groups received vehicle or TQ, respectively. The rectal temperature and behavioral tests including the open field for locomotor activity and rotarod for motor coordination were evaluated. The level of superoxide dismutase (SOD), as well as pathological changes, were also assessed in the striatum region.

Findings/results: No significant differences in rectal temperatures were observed among treated groups. Administration of METH increased locomotor activity and did not change motor coordination. TQ co-administration with METH significantly reduced the central and total locomotion and the mean latency to fall off the rotarod in a dose-dependent manner compared with the METH group. TQ also alleviated the METH-induced decrease in the activity of SOD.TQ, especially at the high dose, reduced the METH-induced reactive gliosis level.

Conclusion and implications: In conclusion, TQ prevents the enhanced locomotor activity, antioxidant impairment, and morphological striatal damage caused by METH in mice. TQ may be a potential candidate for the treatment of specific METH-induced brain disorders or neurological diseases.

Keywords: Adverse drug effects; Methamphetamine; Nervous system; Nigella sativa; Substance abuse; Thymoquinone.

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Conflict of interest statement

The authors declared no conflicts of interest in this study.

Figures

Fig. 1
Fig. 1
The effect of methamphetamine and TQ on motor coordination of mice in the rotarod test. Mice received intraperitoneal methamphetamine (10 mg/kg) four times a day in 2-h intervals and TQ at 5, 10, and 20 mg/kg, 30 min before each methamphetamine injection. The results are presented as mean ± SEM, n = 6. ***P < 0.001 Indicates significant difference compared to the control group; and ###P < 0.001 versus the vehicle + methamphetamine group. TQ, Thymoquinone.
Fig. 2
Fig. 2
Effect of methamphetamine and TQ on the (A) total and (B) central locomotion in the open field test. Mice received intraperitoneal methamphetamine (10 mg/kg) four times a day in 2-h intervals and TQ at 5, 10, and 20 mg/kg, 30 min before each METH injection. The results are presented as mean ± SEM, n = 6. **P < 0.01 and ***P < 0.001 indicate significant differences compared to the control group; and #P < 0.05, ##P < 0.01, and ###P < 0.001 against the vehicle + methamphetamine group. The median of groups was analyzed by Kruskal-Wa Wallis followed by the Dunn test. TQ, Thymoquinone.
Fig. 3
Fig. 3
Effect of methamphetamine and TQ on SOD enzyme activity in the striatum region. Mice received intraperitoneal methamphetamine (10 mg/kg) four times a day in 2-h intervals and TQ at 5, 10, and 20 mg/kg, 30 min before each methamphetamine injection. The results are presented as mean ± SEM, n = 3. ***P < 0.001 Indicates significant differences compared to the control group; and #P < 0.05 and ###P < 0.001 against the vehicle + methamphetamine group. TQ, Thymoquinone, SOD, superoxide dismutase.
Fig. 4
Fig. 4
Effect of methamphetamine and TQ on GSH content in the striatum region. Mice received intraperitoneal methamphetamine (10 mg/kg) four times a day in 2-h intervals and TQ at 5, 10, and 20 mg/kg, 30 min before each methamphetamine injection. The results are presented as mean ± SEM, n = 6. ***P < 0.001 Indicates significant differences compared to the control group; and #P < 0.05 and ###P < 0.001 against the vehicle + methamphetamine group. GSH, Reduced glutathione; TQ, thymoquinone.
Fig. 5
Fig. 5
Light photomicrograph of hematoxylin and eosin-stained sections of the mice striatum that were exposed to different doses of METH and TQ (original magnification 400×). Mice received intraperitoneal METH (10 mg/kg) four times a day in 2-h intervals and TQ at 5, 10, and 20 mg/kg, 30 min before each METH injection. Arrows indicate Rosenthal fibers. (A) Control group, no gliosis; (B) TQ at 20 mg/kg, no gliosis; (C) METH, high grad gliosis; (D) METH + TQ 5 mg/kg, high grad gliosis; (E) METH + TQ 10 mg/kg, moderate gliosis; (F) METH + TQ 20 mg/kg, mild gliosis. METH, Methamphetamine; TQ, thymoquinone
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