The ineffectiveness of extinction therapy is likely due to the context dependence of extinction ( Bouton and King, 1983 Kearns and Weiss, 2007), such that when extinction therapy is conducted in a clinical setting, it is not likely to transfer to the drug-taking context to prevent cue-induced relapse.Ī pharmacological enhancement of the consolidation of extinction memory is one mechanism by which the context specificity of extinction might be reduced. Extinction can reduce responses to drug cues, but clinical studies using extinction therapy have reported little success ( Conklin and Tiffany, 2002). Extinction does not cause “forgetting” of the original stimulus–reward relationship ( Bouton, 2004). Extinction is an active process where an organism learns that a stimulus is no longer predictive of reward, and therefore, future presentations of the stimulus no longer produce behaviors to seek that reward. Extinction of drug-associated cues has been proposed as a means of reducing the motivational properties of cues to prevent relapse ( O'Brien et al., 1990 Taylor et al., 2009). A pharmacological method that can render extinction context independent may provide an innovative method to reduce cue-induced relapse in addicts and to study the neurobiology of addiction.ĭrug addiction is a chronic relapsing disorder, consisting of periods of abstinence followed by relapse to drug use, often initiated by exposure to drug-associated cues ( Shaham et al., 2003). DCS treatment caused a reduction in cue-induced reinstatement only when it was given after cue extinction sessions, and not when given 1) in the absence of extinction or 2) after a brief memory reactivation session. The effect of systemic DCS was recapitulated by administration of DCS into the nucleus accumbens core, but not in the basolateral amygdala, dorsal hippocampus, infralimbic or prelimbic prefrontal cortex. We demonstrate that DCS given postextinction session in context B reduces reinstatement in context A, indicating a reduction in the context specificity of extinction learning. DCS was administered systemically or into a specific brain region immediately following the cue extinction sessions to enhance the consolidation of extinction learning. The cue was later extinguished in the drug-taking context (context A) or a novel context (context B) using a Pavlovian cue extinction procedure designed to mimic human cue exposure therapy. Male Sprague Dawley rats were trained to self-administer cocaine associated with a cue. We tested the hypothesis that d-cycloserine (DCS), which enhances extinction in other procedures, would enhance extinction of cocaine-associated cues in a novel context to reduce cue-induced reinstatement. Cue extinction therapy, however, takes place in a novel context (e.g., treatment facility), and is unlikely to be effective due to the context specificity of extinction.
Extinction therapy has been proposed as a method to reduce the motivational impact of drug-associated cues to prevent relapse.
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