Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area

Kuo, Chi-Chung; Shen, Hui; Harvey, Brandon K.; Yu, Seong‐Jin; Kopajtic, Theresa; Hinkle, Josh J.; Kyrkanides, Stephanos; Katz, Jonathan L.; Wang, Yun

doi:10.1007/s00213-015-4134-4

Cited by 12 publications

(7 citation statements)

References 52 publications

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“…Meth sensitization was induced in mice after repeated administration of Meth ( n = 16, sensitizing dose, 2.5 mg/kg/day, s.c.) for 7 days (days 0 to 6, see timeline, Fig. 1A ) 34 . Control noS animals received a daily saline injection ( n = 22, s.c., × 7 days).…”

Section: Resultsmentioning

confidence: 99%

Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens

Chen

et al. 2021

Cell Transplant

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Amphetamine-type stimulants have become important and popular abused drugs worldwide. Methamphetamine (Meth) sensitization, characterized by a progressive increase in behavioral responses after repeated administration, has been reported in rodents and patients. This behavioral effect has been used as a laboratory model to study drug addiction and schizophrenia. The mesolimbic dopaminergic pathway plays a significant role in the development of Meth behavioral sensitization. Previous studies have reported that the ablation of nucleus accumbens (NAc) by electrolytic or thermal lesioning attenuates addictive behavior to opioids in animals. However, these studies were only conducted in opioid addictive rodents. Furthermore, these ablation procedures also damaged the non-dopaminergic neurons and fibers passing through the NAc. The purpose of this study was to examine the therapeutic effect of NAc lesioning by a selective dopaminergic toxin in Meth-sensitized animals. Adult mice received repeated administration of Meth for 7 days. Open-field locomotor activity and stereotype behavior were significantly increased after Meth treatment, suggesting behavior sensitization. A partial lesion of dopaminergic terminals was made through stereotaxic administration of dopaminergic toxin 6-hydroxydopamine (6-OHDA) to the NAc in the Meth -sensitized mice. Meth behavioral sensitization was significantly antagonized after the lesioning. Brain tissue was collected for qRT-PCR analysis. Repeated administration of Meth increased the expression of tyrosine hydroxylase (TH), BDNF, and Shati, a marker for Meth sensitization, in the NAc. Treatment with 6-OHDA significantly antagonized the upregulation of TH and Shati. Taken together, these data suggest that local administration of 6-OHDA mitigated Meth sensitization in chronic Meth-treated animals. Our data support a new surgical treatment strategy for Meth abuse.

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Section: Resultsmentioning

confidence: 99%

Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens

Chen

et al. 2021

Cell Transplant

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“…Crossing the central squares by METH-treated mice more than the control group implied that had an anxiety-like behavior. It has been reported that METH-induced behavioral sensitization occurs after repeated administration in rodents ( 17 ). In line with our results, Struntz and Siegel reported increased locomotor activity and anxiety-like behavior in adult mice that were treated with a single low dose METH, 4 mg/kg ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

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

Roohbakhsh

Moshiri

Kakhki

et al. 2021

Research in Pharmaceutical Sciences

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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.

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“…Shen found that repeated METH administration initiated behavioral sensitization in wild-type mice, and these changes were attenuated in μ-opioid knockout mice, suggesting that MORs regulate behavioral sensitization of METH Shen et al (2010), which is consistent with Kuo's findings that the role of the u-opioid receptor is associated with its location in the brain. Using a stereotactic injection technique, AAV-MORs was injected into the NAc or the ventral tegmental area (VTA) of adult mice and MORs overexpression in NAc and VTA differentially affected METH sensitization, with MORs in VTA enhancing behavioral sensitization while MORs in the NAc region had an antagonistic effect (Kuo et al, 2016). Mounting evidence suggests that neuroplasticity changes are related to behavioral sensitization.…”

Section: Behavioral Sensitization and Cross-sensitizationmentioning

confidence: 99%

The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review

Liu

Zhang

et al. 2021

Front. Pharmacol.

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Abuse of methamphetamine (METH), an illicit psychostimulant, is a growing public health issue. METH abuse during pregnancy is on the rise due to its stimulant, anorectic, and hallucinogenic properties. METH can lead to multiple organ toxicity in adults, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity. It can also cross the placental barrier and have long-lasting effects on the fetus. This review summarizes neurotoxicity, cardiovascular toxicity, hepatotoxicity, toxicity in other organs, and biomonitoring of prenatal METH exposure, as well as the possible emergence of sensitization associated with METH. We proposed the importance of gut microbiota in studying prenatal METH exposure. There is rising evidence of the adverse effects of METH exposure during pregnancy, which are of significant concern.

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Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area

Abstract: Our data suggest a differential modulation of Meth sensitization by overexpression of MOR in NAc and VTA. Regional manipulation of MOR expression through AAV may be a novel approach to control Meth abuse and psychomimetic activity.

Cited by 12 publications

References 52 publications

Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens

Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens

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

The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review

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