Recently abstinent methamphetamine (Meth) abusers showed neurovascular dysregulation within the striatum. In this article, the study attempted to discover the factors contributing to dysregulation and why these effects persist. In rats, micro–computed tomography revealed a marked reduction in vessel diameter and vascular volume uniquely within the striatum between 1 and 28 days after Meth self-administration. Subsequently, it was determined that dopamine (DA) D2 receptors regulated Meth-induced striatal vasoconstriction, and that acute Meth exposure also increased striatal levels of endothelin receptor A and decreased neuronal nitric oxide synthase. Collectively, the data provide evidence that Meth-induced striatal neurovascular dysregulation involves DA receptor signaling that results in vasoconstriction via endothelin receptor A and nitric oxide signaling. As these effects can lead to hypoxia and trigger neuronal damage, these findings provide a mechanistic explanation for the selective striatal toxicity observed in the brains of Meth-abusing humans.
See article at J Pharmacol Exp Ther 2014, 351:432–439.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics