How Do We Become Tolerant to Opiates? An Animal Study

Dopaminergic neurons in the ventral tegmental area (VTA) are central mediators of reward from various substances. These investigators examined reward tolerance, VTA size, and a primary signal transduction pathway in dopaminergic VTA neurons in drug-naïve rats and rats made tolerant to opiates by implantation of morphine pellets for 5 days. The pathway involves insulin receptor substrate 2 (IRS2) protein and Akt (also called protein kinase B) and has been implicated in apoptosis.

One day after morphine was withdrawn, the size of VTA dopaminergic neurons was reduced, but cell survival and activity downstream of the IRS2-Akt pathway were not. (Neuronal size also decreased in a second group of rats that had self-administered heroin.) These chang…