From actions to habits: neuroadaptations leading to dependence

Alcohol Research & Health, Winter, 2008 by Henry H. Yin

Addiction is a series of misguided actions. Yet how the brain selects and generates actions has received surprisingly little attention in addiction research. In recent years, considerable progress has been made in identifying the neural circuits responsible for the control of goal-directed actions and habit formation. It is becoming increasingly clear that drugs of abuse can alter these neural pathways. This article discusses the mechanisms underlying reward-guided action selection and their implications for research on alcohol addiction.

THE ORGANIZATION OF CORTICO-BASAL GANGLIA NETWORKS

Understanding how the brain generates actions must begin with a discussion of the cortico-basal ganglia networks. (1) These networks form a hierarchy for motivated behavior (Swanson 2000; Yin and Knowlton 2005, 2006), which consists of variations on a basic motif, a prototypical network critical for behavioral selection. In this network, glutamatergic (excitatory) projection neurons from the cerebral cortex, a highly layered structure, send axons to the nuclei underneath, commonly known as the basal ganglia, which contain f-aminobutyric acid (GABA)ergic (inhibitory) projection neurons. The inhibitory outputs from the basal ganglia, in turn, are directed at downstream structures in the brainstem and in various thalamic nuclei whose projections reenter the cortex.

There is reason to believe that the basal ganglia circuits and their intrinsically generated oscillations are responsible for the generation and selection of behavioral programs; and the variations in patterns of connectivity and in the expression of key proteins like membrane receptors may be tailored for different types of global control processes, as described below (Gerdeman et al. 2003; Yin and Knowlton 2006).

A striking feature of such control processes is that they can be measured behaviorally using specific tests.

As recent research has shown, normal mechanisms of learning and memory are usurped by exposure to addictive drugs, so that instead of serving normal biological needs they defect to the purpose of drug seeking (Hyman et al. 2006). There is no consensus, however, on precisely what type of learning process is usurped by addictive substances. Current hypotheses focus on the enhancement of craving, or incentive sensitization (Robinson and Berridge 2003), and on the avoidance of harmful consequences of withdrawal, or allostasis (Le Moal and Koob 2007). These hypotheses largely neglect the central issue of how actions are selected. One reason for this neglect is that the chief behavioral measures in the field (e.g., self-administration and conditioned place preference (2)) lack sufficient analytical power to isolate contributions of distinct neural networks. As discussed below, a major challenge in addiction research is to understand the mechanisms underlying these behavioral control processes and how they are affected by exposure to alcohol and other drugs.

THREE MODES OF BEHAVIORAL CONTROL

What, then, are these control processes and why are they so important for understanding alcohol addiction? In the study of behavior guided by rewards (i.e., appetitive behavior), researchers are now able to distinguish three major modes of behavioral control with simple experimental tests. These three modes are Pavlovian approach, (3) goal-directed action, and habit. Although these are rather broad classes of behavioral control with simple operational definitions, they shed considerable light on the integrative functions of the cortico-basal ganglia networks.

Preparatory appetitive Pavlovian behaviors (e.g., approaching location of reward and stimuli that predict reward) and goal-directed instrumental actions are both controlled by the anticipation of the reward. For both, reducing the value of the reward (e.g., by selective satiety, in which the animal is sated on the particular reward offered but not other rewards) or taste aversion induction (in which a particular food is paired with an injection of lithium chloride that results in gastric discomfort) can reduce performance (Colwill and Rescorla 1985; Yin and Knowlton 2002). In both, too, performance is controlled by a predictor of reward and the reward itself. But for Pavlovian approach, the predictor of reward is a stimulus arranged by the experimenter and entirely independent of the animal's behavior, whereas in instrumental behavior the predictor is the self-generated action by the animal. This distinction is revealed by direct manipulation of the postulated contingencies (e.g., increasing the probability of reward independent of the predictor, be it a particular action in the case of instrumental learning or a stimulus in the case of Pavlovian conditioning) (Hammond 1980; Schwartz and Gamzu 1977). Manipulating the relationship between stimulus and outcome specifically affects Pavlovian behavior, whereas manipulating the action-outcome relationship specifically affects instrumental behavior (Dickinson 1994, 1997; Schwartz and Gamzu 1977).