What is craving? Models and implications for treatment

Abstract

Although many alcoholics experience craving, researchers have not yet developed a common, valid definition of the phenomenon. Numerous models of the mechanisms underlying craving have been suggested, however. One of those models--the neuroadaptive model--suggests that the prolonged presence of alcohol induces changes in brain-cell function. In the absence of alcohol, those changes cause an imbalance in brain activity that results in craving. Furthermore, the adaptive changes generate memories of alcohol's pleasant effects that can be activated when alcohol-related environmental stimuli are encountered, even after prolonged abstinence, thereby leading to relapse. Similarly, stressful situations may trigger memories of the relief afforded by alcohol, which could also lead to relapse. Neurobiological and brain-imaging studies have identified numerous brain chemicals and brain regions that may be involved in craving. Psychiatric conditions that affect some of these brain regions, such as depression or anxiety, also may influence craving. A better understanding and more reliable assessment of craving may help clinicians tailor treatment to the specific needs of each patient, thereby reducing the risk of relapse.

Figure 1

The neuroadaptive model of craving. This model proposes that chronic alcohol exposure leads to changes in brain cell function (i.e., sensitization, or neuroadaptation) that are expressed as changes in the activity of various brain chemicals (i.e., neurotransmitters), such as dopamine, glutamate, gamma-aminobutyric acid (GABA), and endogenous opioids. Neuroadaptation can contribute to certain characteristics of alcohol dependence, such as withdrawal, and to the development of a reward memory—that is, the memory of the importance of alcohol or alcohol-related stimuli to the drinker’s well-being. During initial abstinence, when alcohol withdrawal may occur, neuroadaptation leads to an imbalance in brain function, which results in subjective feelings of discomfort and, subsequently, craving. During prolonged abstinence, situations or stimuli previously associated with alcohol consumption may activate the reward memory, thereby also inducing craving. Craving, in turn, may result in relapse to drinking. Stress, which on a chemical level is mediated by the neurotransmitter serotonin, can enhance neuroadaptation as well as trigger the reward memory.

Figure 2

Brain regions involved in craving. Alcohol activates the nucleus accumbens, the brain’s “reward center.” Nerve cells (i.e., neurons) in the nucleus accumbens send information to the amygdala, which plays a role in the modulation of stress and emotions; the frontal cortex (shaded area), including the dorsal lateral prefrontal cortex (DLPC), where the reward memory is thought to be located; and the basal ganglia, which plays a role in repetitive thought and behavior patterns. Neurons located in the amygdala also send information to the DLPC and the basal ganglia. The DLPC sends information back to the basal ganglia (a connection that may play a role in obsessive-compulsive behaviors) and to the nucleus accumbens. Feedback from the DLPC to the nucleus accumbens may sensitize the latter to further alcohol exposure. The DLPC itself is controlled by the orbitofrontal cortex, which induces impulse control.