1. Mice treated with single-walled carbon nanotubes (SWNTs) self-administered less methamphetamine (METH) and showed a decrease in craving and relapse.
2. SWNTs acted by attenuating the METH-induced increase in dopamine production.
Evidence Rating Level: 2 (Good)
Study Rundown: METH increases the release of dopamine in the prefrontal cortex and striatum, leading to addiction and altering other goal-directed motivational behaviors. Because SWNTs have been previously found to be neuroprotective in mouse models of Alzheimer’s disease, the researchers in this study tested the ability of SWNTs to treat METH addiction and normalize dopamine levels.
After injecting either individual (iSWNT) or aggregated (aSWNT) formulations into the brains of mice, no alteration in behavior or brain morphology was noted, indicating that the treatment method was safe. The effect of iSWNTs and aSWNTs on METH self-administration was tested, and mice given aSWNTs ceased METH self-administration during a 3-hour test session. When mice were given METH and withdrawn from it, and then treated with aSWNTs, no drug relapse occurred over a period of 3 days. In addition, aSWNTs were able to decrease the craving for METH. Studies to determine mechanism of action showed that aSWNTs decreased dopamine production.
This study provides the first evidence of the benefit of using aSWNTs to treat addiction to METH. The efficacy of this treatment in humans as well as its other potential effects still need to be tested. Additionally, other possible modes of administration besides direct injection to the brain need to be developed.
In-Depth [animal study]: Two forms of SWNTs were assessed, iSWNTs which were individual nanotubes, and aSWNTs which were aggregated bundles of nanotubes. 1-2 ng of iSWNTs or aSWNTs were injected into the lateral cerebral ventricle of mice. Their toxicity was assessed by histological staining of the prefrontal cortex and immunostaining of the mesolimbic dopamine system components. No significant alterations in either the brain structure or behavior of the mice were noted.
Treatment with aSWNTs, but not iSWNTs, significantly decreased METH self-administration for 3 hours when compared to vehicle control (p<0.05). To test the effects of aSWNTs on relapse, the mice were administered METH, withdrawn from it for 3 weeks, and then re-exposed to the same drug associated stimuli. When treated with aSWNTs prior to stimulus re-exposure, the mice did not self-administer METH for at least 3 days (p<0.001 compared to vehicle control). The conditioned place preference model was used to show that aSWNTs were able to decrease cravings and drug relapse after 10 days of withdrawal from METH (p<0.001).
Mechanism of action studies showed that administration of aSWNTs with METH resulted in a significant decrease in striatum dopamine levels compared to vehicle control (p<0.01). Western blots showed that expression levels of tyrosine hydroxylase, an enzyme involved in dopamine production, were significantly reduced by aSWNTs (p<0.001). Finally, since METH increases synaptic density in the striatum and prefrontal cortex, electron microscopy and Western blotting were used to show that aSWNTs significantly decreased the presence of synapses (p<0.001).
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