Overview and historical perspective of four papers presented on research related to the endogenous opioid system

摘要

The endogenous opioid system is now known to play a major role in many aspects of normal physiology and neurobiology, as well as a central role in many of the addictive disease disorders. There are many areas of ongoing exciting research regarding this diverse system, including some new approaches to understanding both the brain localization and specific molecular mechanisms underlying behaviors. These include the use of small interfering RNA directed against the mu opioid receptor system, which when instilled in the substantia nigra-ventral tegmental area has been shown to result in both an ablation of heroin-induced locomotor activity and conditioned place preference. Further, a wide variety of human molecular genetics studies identify the mu opioid receptor as an important contributor to the vulnerability to develop an addiction, as well as a gene whose functional variants may alter physiological and pathological states in a wide variety of ways (e.g., Levran et al., 2008; Nielsen et al, 2008; Zhang et al., 2009). When research first began at The Rockefeller University in 1964 to attempt to develop a pharmacological treatment for opiate addiction, it was conceptualized that a therapeutic agent should be- targeted to a specific site of action of opiate drugs like heroin and its active metabolites, primarily morphine (Dole et al., 1966). Further, the probable existence of specific "opiate (later opioid) receptors" was postulated, a concept that had been introduced by a few different groups, including that of the late Martin in Kentucky, and Collier and colleagues in England. Thus, in the selection of a pharmacological agent, criteria were set that it should be orally effective, long-acting, and targeted at what was then simply called "the opiate receptor," and, of course, methadone was the agent chosen (Dole etal., 1966).