Neuroadaptational Views of Addiction

Allostasis and Neuroadaptation

More recently, opponent process theory has been expanded into the domains of the neurocircuitry and neurobiology of drug addiction from a physiological perspective. An allostatic model of the brain motivational systems has been proposed to explain the persistent changes in motivation that are associated with vulnerability to relapse in addiction, and this model may generalize to other psychopathologies associated with dysregulated motivational systems. Allostasis from the addiction perspective has been defined as the process of maintaining apparent reward function stability through changes in brain reward mechanisms (Koob and Le Moal, 2001). The allostatic state represents a chronic deviation of brain reward set point that is often not overtly observed while the individual is actively taking the drug. Thus, the allostatic view is that not only does the b-process get larger with repeated drug taking, but the reward set point from which the a-process and b-process are anchored gradually moves downward, creating an allostatic state (Figure 1.12).

The allostatic state is fueled by the dysregulation of neurochemical elements of brain reward circuits and activation of brain and hormonal stress responses. It is currently unknown whether this hypothesized reward dysfunction is drug-specific and common to all addictions. The established anatomical connections and manifestation of this allostatic state as compulsive drug taking and loss of control over drug intake are critically based on dysregulation of specific neurotransmitter function in the neurocircuits of the ventral striatum and extended amygdala (see Introduction to the Neuropsychopharmacology of Drug Addiction). Chronic elevation in reward thresholds is viewed as a key element in the development of addiction that sets up other self-regulation failures and persistent vulnerability to relapse during protracted abstinence. The view that drug addiction and alcoholism are the pathology that results from an allostatic mechanism that usurps the circuits established for natural rewards provides an approach to identifying the neurobiological factors that produce the vulnerability to addiction and relapse.

FIGURE 1.12 Diagram illustrating an extension of the Solomon and Corbit (1974) opponent-process model of motivation to outline the conceptual framework of the allostatic hypothesis. Both panels represent the affective response to the presentation of a drug. (Top) This diagram represents the initial experience of a drug with no prior drug history. The a-process represents a positive hedonic or positive mood state, and the b-process represents the negative hedonic or negative mood state. The affective stimulus (state) has been argued to be a sum of both an a-process and a b-process. An individual who experiences a positive hedonic mood state from a drug of abuse with sufficient time between re-administering the drug is hypothesized to retain the a-process. In other words, an appropriate counteradaptive opponent-process (b-process) that balances the activational process (a-process) does not lead to an allostatic state. (Bottom) The changes in the affective stimulus (state) in an individual with repeated frequent drug use that may represent a transition to an allostatic state in the brain reward systems and, by extrapolation, a transition to addiction. The apparent b-process never returns to the original homeostatic level before drug taking is reinitiated, thus creating a greater and greater allostatic state in the brain reward system. The counteradaptive opponent-process (b-process) does not balance the activational process (a-process) but in fact shows residual hysteresis. Although these changes are exaggerated and condensed over time in the present conceptualization, the hypothesis is that even after detoxification during a period of prolonged abstinence, the reward system is still bearing allostatic changes. In the nondependent state, reward experiences are normal, and the brain stress systems are not greatly engaged. During the transition to the state known as addiction, the brain reward system is in a major underactivated state while the brain stress system is highly activated. The following definitions apply: allostasis, the process of achieving stability through change; allostatic state, a state of chronic deviation of the regulatory system from its normal (homeostatic) operating level; allostatic load, the cost to the brain and body of the deviation, accumulating over time, and reflecting in many cases pathological states and accumulation of damage. [Taken with permission from Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 2001, (24), 97–129.]

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