study published in Nature showed an upregulation of microRNA-212 in the dorsal striatum of rats previously exposed to cocaine for extended periods. Animals infected with a viral vector overexpressing miR-212 in the dorsal striatum produced the same initial levels of cocaine intake; however, drug consumption progressively decreased as net cocaine exposure increased. The authors of the study noted that viral-infected animals exhibited decreased operant responding during the post-infusion time-out period and proposed that this demonstrated a reduction in compulsive drug-seeking behavior.(Hollander et al.) miR-212 acts through Raf1 to enhance the CREB response; CREB-TORC is known to negatively regulate the reinforcing effects of cocaine. (Hollander et al.) This study provides one example (miR-212, owing to its amplification of CREB) of a self-administration study that may provide potential therapeutic targets for the treatment of cocaine addiction. One of the most important advances to emerge from self-administration studies comes from a behavioral model for addiction in animals. This model relies on observation of three separate phenomena to classify a rat as “addicted:” 1) Persistence in drug-seeking'': Depends on the attempts of rats to obtain drug during time-out or no-periods in the self-administration apparatus. 2) Resistance to punishment: Measured by how much rats maintain rates of self-administration when cocaine infusion is paired with an electric shock. 3) Motivation for the drug''': Measured by the breakpoint in progressive ratio reinforcement. (Deroche-Gamonet et al.) The researchers used an additional test to further support the classification of a rat as “addicted” by measuring relapse rates during reinstatement paradigms. Human drug addicts reportedly relapse at a rate of >90% as measured from the initial diagnosis. Rats that responded at high rates after some form of cue-induced reinstatement could be considered likely to relapse.(Deroche-Gamonet et al.) This model provided an important advancement for the method of self-administration because it allows animal models to better approximate the physiological and behavioral aspects of drug addiction in humans. Self-administration experiments can also be paired with methods such as in vitro electrophysiology or molecular biology to understand the effects of addiction on neural circuitry. Self-administration studies have allowed researchers to locate a staggering number of changes in brain signaling that occur in addiction. One example of such a study involved examining synaptic plasticity in rats undergoing the behavioral shift to addiction. Using the criteria for classifying rats as “addicts” or “non-addicts” as put forth by Deroche-Gamonet et al., it was found that addicted