Miller-The ASAM Principles of Addiction Medicine, 7e

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The Anatomy of Addiction Michael J. Wesley, Colleen A. Hanlon, and Thomas J. R. Beveridge

to eventual substance use disorder (SUD) or addiction, it is critical to understand the neural mechanisms that underlie basic drug reinforcement. Following a basic primer on the neuroanatomy of addiction, Part 2 (Neuroanatomy of Drug Reinforcement) focuses on the systems associated with the primary reinforcing effects of three specific classes of sub stances, namely, psychostimulants, opioids, and cannabinoids. We focus on the site of action, which defines the access points for a drug to influence a specific brain process and highlights the role of the limbic system. In Part 3 (Neuroanatomy of Drug Addiction), we will describe how an initial reinforcing drug action influences brain areas beyond the limbic system, which are involved in habit formation and maintenance of the ini tially reinforced behavior. For the most part, the discussion of the anatomy of rein forcement and addiction maps onto structures associated with the limbic system and the basal ganglia. PRIMER ON NEUROANATOMY The brain is a complex organ with interconnected yet distinct anatomy. When attempting to understand how neuroanatomy relates to behavior in general, and addiction specifically, it is helpful to consider neuroanatomy at various spatial levels of analysis. For example, at the cellular level (on the order of nanometers and micrometers) drugs have direct physiological effects on specific molecular targets according to the topogra phy of a given receptor system. Cellular receptor systems are often a part of pathways that span multiple brain structures. Zooming out several orders of magnitude (on the order of millimeters and centimeters), it is the concerted activity of di verse cellular physiology within a given location (which is not limited to the primary molecular effect of a single drug) that gives rise to the multiple functions of a specific brain struc ture. Thus, it is unlikely that there is a 1:1 relationship between a primary cellular drug effect and the multifaceted behaviors and symptoms of addiction. It is more likely that the coordi nated neural network activity of several brain structures with in a given neural system (which may be heavily influenced by a primary drug effect) is responsible for the many behaviors and symptoms of addiction. While there is still much to learn about the neuroanatomy of addiction, preclinical and clinical research has uncovered multiple cellular systems and brain structures involved in the addiction process. The brain structures most often mentioned in the con text of unhealthy substance use and addiction are closely as sociated with the limbic system, lateral hypothalamus, basal

CHAPTER OUTLINE

■ Introduction ■ Primer on neuroanatomy ■ Neuroanatomy of drug reinforcement ■ Neuroanatomy of drug addiction ■ Moving forward

INTRODUCTION Dr Watson admiring Sherlock Holmes “But consider! Count the cost! Your brain may, as you say, be roused and excited, but it is a pathological and morbid process, which involves increased tissue change and may at least leave permanent weakness…. Why should you, for a mere passing pleasure, risk the loss of those great powers with which you have been endowed?”— Sign of Four , Sherlock Holmes (Arthur Conan Doyle, 1894). This quote from Dr Watson comes as a plea to Sherlock Holmes who has started using cocaine in a “7% solution” when he is feeling bored. This may be one of the first suggestions that regular use of psychostimulants could change the structure of the brain—a fictional assertion from 221B Baker Street, which can now be supported by shelves of brain imaging journals in the nonfiction section of your local university. Over one hundred years later, we now know that chronic use of many commonly used addictive drugs (including but not limited to cocaine, alco hol, nicotine, and opioids) can lead to structural and functional pathology in the brain. This pathology is not restricted to a sin gle brain region, a single cell type, or a single neurotransmitter system. Additionally, the topography of drug-associated neural changes evolves in a spatially progressive manner as the vulner able individual progresses from a set of initially rewarding expe riences to addiction. The temporal continuum of substance use disorder is recognized by the DSM-5, and we are consistently learning more about its neural correlates. There are three primary goals of this chapter. They are (a) introducing the reader to a common set of neural regions, which appear to be critical to the acquisition and maintenance of substance use disorder, (b) discussing changes in these re gions during the initial phases of reward-based learning, and (c) concluding with a discussion of functional and structural neuropathology associated with addiction. Whether we are observing young adults after a high school football game, or rodents in cages in a research laboratory, initial drug taking is nearly always a reinforced behavior. Consequently, in order to understand why certain individuals may be more vulnerable

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