Experimentation Experimentation Abuse Abuse Tolerance Tolerance Withdrawal Withdrawal Stress Distortion of Isolation thinking Preoccupation thinking with drug
Gene induction ¯ BDNF ¯DA
¯ 5HT
Perseveration
Cortical damage
Drinking despite problems Distortion of
Binge Consumption Drug levels Craving
¯ Executive function ¯ Executive function
ADDICTION ADDICTION
FIGURE 4.2. The Spiral of Distress. This model depicts the progression from experimentation to addiction. On the left are criteria for the diagnosis of alcohol dependence. Included are increasing tolerance; alcohol withdrawal due to physical dependence, which increases stress; increasing preoccupation with the drug; spending large amounts of time obtaining and consuming alcohol; and continued use despite negative consequences and problems associated with the use of alcohol. In the middle are known changes in the brain that occur during chronic alcohol use. Changes in gene expression are well documented as occurring during the development of dependence. Studies have shown changes in biogenic amines, particularly serotonin (5 hydroxytryptamine, 5HT) and dopamine, key neurotransmitters involved in dependence (see Crews et al.,1999, for more details). Cortical damage and shrinkage occurs in alcoholics, particularly in frontal and temporal regions. Binge drinking, on the right, is indicative of the behavior most likely to induce tolerance, dependence, and changes in brain structure and function. Loss of biogenic amines could increase craving and drinking. Cortical damage can cause perseveration—the persistence of behavior once the reward is removed—and could be analogous to preoccupation with alcohol. Frontal cortical damage is associated with loss of executive functions and could be related to failure to associate negative consequences with drinking, inability to set goals, and inability to inhibit behaviors, ultimately leading to addiction. Source: Adapted from Koob and Le Moal, 1997.