SAR-39684-the-neurocircuitry-of-illicit-psychostimulant-addiction--an-_020713.pdf

Also summarize the newer and more promising

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also summarize the newer and more promising investigational treatments and approaches. Theories of addiction The transition from drug use to drug dependence is impacted by numerous factors, including genetics, environmental influences (such as stress and early life experiences), and neurochemical and neuroanatomical modifications in the brain that result from repeated drug use. 6,7 Initial drug use can be attributed to the ability of the drug to act as a reward (ie, a pleasurable emotional state or positive reinforcer), which can lead to repeated drug use and dependence. 8,9 A great deal of research has focused on the molecular and neuroanatomical mechanisms of the initial rewarding or reinforcing effect of drugs of abuse. However, more recent research on the long-term neuroanatomical and molecular changes in the brain that result from chronic drug use has revealed drug addiction to be highly complex and involve brain systems beyond the canonical reward circuitry. Several parallel and intersecting theories of drug addiction include changes in behavior that are supported by various alterations in the underlying neurocircuitry of addiction. Robinson and Berridge hypothesized that repeated drug use produces alterations in the brain reward and associative learning systems, such that the drug user becomes increasingly sensitive to both the drug and drug-associated cues, resulting in pathological drug seeking or “wanting.” 10,11 Koob and Le Moal have postulated that repeated drug use and dependence are a result of decreased functioning of the brain’s reward system coupled with an increase in the engagement of the brain’s antireward or stress circuitries. 12,13 These two opposing neurocircuitries are hypothesized to interact in a cyclical manner that ultimately manifests as addiction. 12 Everitt and Robbins have theorized that drug addiction is the result of transitions from initial, voluntary drug use to habitual and eventually compulsive drug use, which results from a switch in the relative engagement of the neurocircuitries underlying these behaviors. 14 Finally, Hyman and colleagues have also suggested has also suggested that addiction is a disorder characterized by the “hijacking” of normal learning and memory processes involved in reward seeking and drug–cue associations. 4 These theories all agree that drug addiction is characterized by a progression or shift from initial stages, where the drug user is in control, to the end stages, where the drug user has lost control over drug use. Furthermore, this continuum of behavioral adaptation is proposed to be mediated by drug- induced alterations in the neurocircuitries underlying reward, executive function, and learning and memory. Despite these recent advances in our understanding of the addicted brain, the majority of FDA-approved treatments for drug addiction aim to intervene at the level of the acute rewarding effects of drugs of abuse.
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