Do Pharmacological Approaches that Prevent Opioid Tolerance Target Different Elements in the Same Regulatory Machinery?

Abstract: In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Muopioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including th