Stages in addiction: a functional magnetic resonance imaging (fMRI) study into the neural mechanisms of chronic and non-chronic alcohol dependence and gambling disorder

Different stages can be distinguished in the development of addiction and the
end stage is currently seen as a chronic or chronic intermitting brain
disorder. In preclinical studies, these different stages are associated with
different neurobiological processes and a variety of mechanisms are proposed to
be responsible for the development of chronicity in addiction. Some animal
models emphasize the change from initial impulsive drug use through the loss of
control over this behavior such that it becomes habitual and eventually
compulsive. According to dual-system accounts of addiction, this shift of
control over behavior is determined by the balance between a goal-directed and
a habitual system. Other animal models highlight the motivational change from
positive reinforcement to negative reinforcement processes in chronic
addiction, although the latter model also explicitly relates to the changes
from impulsive (positive reinforcement) to compulsive use (negative
reinforcement). Human models of changes in the development of addiction stress
the role of loss of control over drug use, and impulsivity has been pinpointed
as an important factor relating both to the development of substance misuse,
and to relapse in chronic addiction. However, compulsivity has been largely
ignored in human research on addiction.

In summary, several mechanisms involved in the shift from non-chronic to
chronic addiction have been proposed in animal models, but almost none of them
have been tested in clinical samples. We want to translate these hypotheses
derived from animal models to the human situation in order to discover what
discerns chronic- from non-chronic addiction in humans. We therefore propose an
fMRI study to investigate the neurobiological differences between chronic and
non-chronic human addicts with either a substance-related addiction (alcohol
dependence) or a behavioral addiction (pathological gambling). These two groups
are selected in order to compare mechanisms in addictive disorders with
neurotoxic effects and addictive disorders without the confounding effects of
neurotoxicity of substances on the brain.

The main aim of the proposal is to study the processes involved in non-chronic
vs. chronic drug seeking behavior in samples of alcohol dependent persons (ADs)
and pathological gamblers (PGs) with different levels of chronicity. We thereby
rely on knowledge derived from animal work and implement tests of impulsivity,
compulsivity, goal-directed and habitual behavior and positive and negative
reinforcement.

Behavioral and neurobiological outcome measures will be used to test how the
level of chronicity is related to goal-directed and habitual behavior and
positive and negative reinforcement. To model the effect of negative
reinforcement on the shift from impulsive to compulsive behavior, as measured
by a habit task, a stress induction vs. neutral control condition (separated by
a 1 week interval) is used.
To induce a physiological stress response participants will be subjected to the
socially evaluated cold-pressor test (SECPT), which is known to relatively
non-intrusively increase salivary cortisol, blood pressure, heart rate and
subjective stress ratings by immersion of the participants* hand for a short
duration into ice water (lukewarm water in control condition). Simultaneously,
participants in the stress condition are monitored by an unfamiliar person and
videotaped.

The risk associated with participation can be considered negligible and the
burden can be considered minimal. Total participation time is approximately 6
hours. Structured diagnostic interviews for psychiatric disorders and
personality questionnaires will be administered.