Miller-The ASAM Principles of Addiction Medicine, 7e

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CHAPTER 3 • The Anatomy of Addiction

ganglia, and frontal cortical regions. Here we present a brief description of each of these systems. Readers interested in a more complete description of the anatomy of these regions are referred to the following reviews. 1-4 Subcortical Limbic System Research into the limbic system has a long and venerable his tory, but some scholars have suggested that the term may have outlived its usefulness. Nonetheless, a brief historic review of the term is a useful way of introducing some of the regions in volved in drug addiction. The term limbic is derived from the Latin term limbus , meaning border, and was used to describe a ring of phylogenetically older cortex that separates the dien cephalon and the neocortex. This limbic lobe consisted of the subcallosal area, cingulate, and parahippocampal gyri ( Fig. 3-1 ). This purely anatomic distinction was expanded by MacLean 5 in 1952 to describe a functional unit that was proposed to be responsible for emotional expression. He made the distinction between the older, medial cortex and the more lateral neocor tex, which is involved in cognitive functions. MacLean’s concept was that most human behavior is the result of cooperation between three systems of the brain. The cerebral cortex is responsible for higher-order reasoning and speech, whereas the limbic system was the source of emotions, aspects of personal identity, and fight-or-flight instincts. The third aspect of MacLean’s system is the reptilian brain. Early work with primates showed that when various parts of the lim bic system were electrically stimulated, a range of emotional

responses was produced, such as rage, fear, and joy. 6 This phy logenetically older brain is responsible for the organism avoid ing things that are “disagreeable” and approaching those that are “agreeable”—reactions that MacLean saw as having sur vival value. It is now clear that structures associated with the limbic system (such as the hypothalamus, hippocampus, and amygdala) are essential not only for learning and memory but also for the emotional context and the affective response to learned associations. As is detailed, many addictive drugs have their sites of ac tion within the limbic system, and the neurochemistry within these structures is altered during the addiction process. This may help explain why decisions surrounding drug seeking and drug taking seem to be driven more by emotion and instinct rather than by logic. From an anatomic perspective, MacLean defined the lim bic system as the original limbic lobe along with other struc tures sharing direct connections with them. These include the olfactory cortex, hippocampal formation, amygdala, septum, hypothalamus, habenula, anterior thalamic nuclei, and parts of the basal ganglia. With further anatomic research, more and more areas were shown to share direct connections with these structures and some of these began to be included in the lim bic system. The result was that the boundaries of the limbic system became overly broad. Brodal 7 observed that the term limbic system was becoming less useful, and he argued that it should be discarded altogether; however, the concept of a phy logenetically older forebrain system responsible for emotional control is now firmly entrenched.

Corpus callosum

Cingulate cortex

Ant. n. of thalamus

Fornix

Septum

Subcallosal region

Olfactory bulb

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Optic chiasm

Hippocampus

Mammillary body

Amygdala

Temporal lobe

Figure 3-1. Regions of the human brain associated with the limbic system, which includes a loop of cortex extending from the subcal losal region through cingulate cortex to the parahippocampal gyrus. Also shown are the hippocampal formation, septum, amygdala, and mammillary bodies.