rats display a prolonged and persistent impairment in mGluR2/3-dependent Long-Term Depression. Despite exposure to the same self-administration paradigm, control rats recovered this form of synaptic plasticity. The authors of the study propose an important explanation for their results in that this specific loss of plasticity over an extended period is responsible for the progressive loss of controlled drug use.(Kasanetz et al.) This represents a potential molecular mechanism by which addicts might differ from non-addicts and undergo pathological learning processes during the development of addiction. Much like animal studies, human experiments that pair self-administration studies with additional neuroscientific techniques provide unique insight into the disease of addiction. Human self-administration studies have gained momentum with the widespread use of fMRI technology to measure BOLD signals. Brain imaging coupled with human self-administration studies with the laboratory have led to the development of a three-stage model of human neurocircuitry of addiction: Binge/Intoxication, Preoccupation/Anticipation, and Withdrawal/Negative Effect. Koob, Lloyd, and Mason reviewed the laboratory models approximating each stage of the model of human addiction.(Koob et al.) The binge-intoxication phase traditionally has been modeled by drug or alcohol self-administration; the psychological effects of addiction might be modeled by the increased motivation for self-administration observed in drug-dependent animals. Self-administration studies capably model the somatic effects of addiction, but many of the most deleterious effects related to drug addiction can be considered psychological in nature. (Koob et al.) Models like the one published by Deroche-Gamonet and colleagues in 2004 better approximate the effects of addiction on physiology and psychology, but animal models are inherently limited in their ability to reproduce human behavior. The use of the self-administration methodology to model human drug addiction provides powerful insight into the physiological and behavioral effects of the disease. While self-administration experiments in humans or animals each pose unique barriers to complete understanding of addiction, the scientific community continues to invest a great deal of effort in both avenues of research in the hopes of improving understanding and treatment of addiction. References Medical treatments Addiction Substance dependence Substance-related disorders Alcohol and health