Important individual differences in the different stages of the addiction process, as well as in the vulnerability to the transition to addiction, have been observed in humans and animals. We reviewed studies demonstrating that the concept of self-regulation combined with the concept of modularity of cognitive function may help to understand individual differences in the vulnerability to drugs and to the transition to addiction. As explained above, there are important individual differences in the different stages of addiction as well as in key brain functions critical for the development of addiction, such as attention, decision-making, reward, emotion, pain, and stress (Crowley et al., 1998
; de Wit et al., 1986
; Deroche-Gamonet et al., 2004
). Flexible, goal-directed behaviors require an adapted cognitive control system for organizing, selecting, and consolidating information resulting from the different modules into a coherent and unified experience (Treisman, 1996
). Neuroanatomical, brain lesion, and site-specific pharmacological modulation studies of the prefrontal cortex have revealed the heterogeneity of the prefrontal cortex and the high functional specialization of its different subregions (Robbins, 2000
). The prefrontal cortex and its different subregions target the main sources of all neurotransmitter systems and have been hypothesized to represent this cognitive control system (Baddeley, 1996
; Robbins, 2000
; Ridderinkhof et al., 2004
, Goldman-Rakic, 1987
We suggest that the concept of self-regulation, combined with the concept of modularity of cognitive function, may help to understand the neural basis of the individual differences in the vulnerability to drug addiction. Indeed, dysfunction of a specific subregion of the prefrontal cortex may lead to loss of control over a specific module, leading, for instance, to a sensitization of insentive salience in one individual and to a hyperreactivity of the stress system in another individual. Therefore, the failure of a specific module may differ from one individual to another and may represent a neuropsychobiological mechanism underlying individual differences in the vulnerability to drug addiction.
Several key potential modules may be identified, including the incentive salience mesolimbic dopamine system module, stress/HPA axis module, habit/striatum module, negative emotional state/extended amygdala module, pain/spinothalamocortical module, and the decision-making/prefrontal cortex module. Such modules are driven by bottom-up signals from both the external world and interoceptive signals and by top-down signals from higher-order system mediating cognitive control. It is important to note that the modules described in this review do not correspond fully to the concept originally defined by Jerry Fodor (1983)
. One of the essential defining features of a Fodorian module is functional autonomy; that is, its function is little, if any, controlled by top-down cognitive control. In contrast, the brain systems identified here are hypothesized to be under tight top-down control by the prefrontal cortex, at least initially before the transition to addiction. These systems are not modular in the strong sense defined by Fodor but begin to resemble to Fodorian modules only after the transition to addiction.
The present multi-system framework may be useful to better understand the different patterns of drug addiction across different individuals and different drugs. It can be hypothesized that individuals with increased sensitivity of the incentive salience mesolimbic dopamine system module and the habit/striatum system may be particularly vulnerable to cocaine and methampetamine abuse through an overvaluation of drug reward and drug-related cues during the binge/intoxication and preoccupation/anticipation
stages Wise 2002
; Jentsch and Taylor 1999
). Individual differences in the function of the incentive salience mesolimbic dopamine system and the habit/striatum modules may be particularly important for craving-type 1 (or reward craving) defined as craving for the rewarding effects of drugs and usually induced by stimuli that have been paired with drug self-administration such as environmental cues, as opposed to craving-type 2 (or withdrawal relief craving) which is conceptualized as an excessive motivation for the drug to obtain relief from a state change characterized by anxiety and dysphoria after protracted abstinence (Heinz et al., 2003
). Individual differences in the pain/spinothalamocortical module may be key for the transition to opiate and alcohol dependence. Decreased sensitivity of the pain system is associated with a higher vulnerability for opiate dependence (Lehofer et al., 1997), whereas hyperactivity of the pain system may predict cue-induced craving in abstinent opiate abusers (Ren et al., 2009). Moreover, considering the importance of the endogenous opiate system in alcoholism, it is likely that vulnerability of the pain/spinothalamocortical or spinoparabrachial module (Besson, 1999
) might be a risk factor for the development of alcoholism and dependence on other drugs (Herz, 1997
). Hyperactivity of the negative emotional state/extended amygdala module is associated with increased emotional pain and stress and might be a risk factor for drug use as a self-medication for emotional pain, dysphoria, and stress (Khantzian et al., 1997
). Vulnerability in the pain/spinothalamocortical module may lead to increased physical and emotional pain during withdrawal and intense craving-type 2, thus contributing to the preponderant role of the withdrawal/negative affect
stage that characterizes opiate and alcohol addiction. Increased reactivity of the stress/HPA axis module may be critical in the initiation of drug intake and for the maintenance of drugs that have little initial rewarding value, such as nicotine, as it potentiates the reinforcing effects of drugs (Piazza and Le Moal, 1998
). Vulnerability of the stress/HPA axis and the negative emotional state/extended amygdala module may contribute to the different patterns of tobacco smoking behavior. Indeed, individuals who smoke regularly but who will always limit their tobacco intake (“chippers”) show no signs of withdrawal and report less stress and better stress coping responses than subjects dependent on tobacco (Shiffman, 1989
) suggesting that hyperaactivity of the stress/HPA axis and the negative emotional state/extended amygdala module may underlie the differences between chippers and dependent smokers. Finally, hypoactivity of the decision-making/prefrontal cortex module may lead to a loss of control over drug intake despite negative consequence because of impaired inhibitory control and decision-making leading to choices of immediate rewards over delayed rewards (Goldstein and Volkow, 2002
). Although the initial failure of a specific module might be specific to one stage of the addiction cycle and to a specific drug, in a given individual the transition to addiction is ultimately likely to be associated with a progressive and generalized loss of control over many, if not all, cognitive modules.