Abstract
BackgroundCocaine addiction is characterized as a chronically relapsing disorder. It is believed that cues present during self-administration become learned and increase the probability that relapse will occur when they are confronted during abstinence. However, the way in which relapse-inducing cues are interpreted by the user has remained elusive. Recent theories of addiction posit that relapse-inducing cues cause relapse habitually or automatically, bypassing processing information related to the consequences of relapse. Alternatively, other theories hypothesize that relapse-inducing cues produce an expectation of the drug's consequences, designated as goal-directed relapse. Discrete discriminative stimuli signaling the availability of cocaine produce robust cue-induced responding after thirty days of abstinence. However, it is not known whether cue-induced responding is a goal-directed action or habit.Methodology/Principal FindingsWe tested whether cue-induced responding is a goal-directed action or habit by explicitly pairing or unpairing cocaine with LiCl-induced sickness (n = 7/group), thereby decreasing or not altering the value of cocaine, respectively. Following thirty days of abstinence, no difference in responding between groups was found when animals were reintroduced to the self-administration environment alone, indicating habitual behavior. However, upon discriminative stimulus presentations, cocaine-sickness paired animals exhibited decreased cue-induced responding relative to unpaired controls, indicating goal-directed behavior. In spite of the difference between groups revealed during abstinent testing, no differences were found between groups when animals were under the influence of cocaine.Conclusions/SignificanceUnexpectedly, both habitual and goal-directed responding occurred during abstinent testing. Furthermore, habitual or goal-directed responding may have been induced by cues that differed in their correlation with the cocaine infusion. Non-discriminative stimulus cues were weak correlates of the infusion, which failed to evoke a representation of the value of cocaine and led to habitual behavior. However, the discriminative stimulus–nearly perfectly correlated with the infusion–likely evoked a representation of the value of the infusion and led to goal-directed behavior. These data indicate that abstinent cue-induced responding is multifaceted, dynamically engendering habitual or goal-directed behavior. Moreover, since goal-directed behavior terminated habitual behavior during testing, therapeutic approaches aimed at reducing the perceived value of cocaine in addicted individuals may reduce the capacity of cues to induce relapse.
Highlights
One of the most insidious characteristics of cocaine addiction is its chronic relapsing nature [1]
Given that cocaine addiction is associated with a high risk of relapse despite negative consequences of returning to drug use such as sickness, depression, or loss of employment [1], it is reasonable to hypothesize that cue-elicited relapse is a habitual behavior
Distinguishing between goal-directed and habitual responding can be accomplished by manipulation of the response outcome [7], cocaine
Summary
One of the most insidious characteristics of cocaine addiction is its chronic relapsing nature [1]. Either of two methods, satiation of the reward or pairing the reward with an unpleasant outcome such as sickness, reduce the reward’s ‘‘value’’ to the animal [7] If either of these methods reduces the number of responses emitted in order to earn the reward in the devalued relative to the normal valued reward group, the behavior is interpreted as a goal-directed action. Other theories hypothesize that relapse-inducing cues produce an expectation of the drug’s consequences, designated as goal-directed relapse. Discrete discriminative stimuli signaling the availability of cocaine produce robust cue-induced responding after thirty days of abstinence. It is not known whether cue-induced responding is a goal-directed action or habit
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