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Appetitive Pavlovian conditioning plays a crucial role in the pathogenesis of drug addiction and conditioned reward cues can trigger craving and relapse even after long phases of abstinence. Promising preclinical work showed that the NMDA-receptor partial agonist D-cycloserine (DCS) facilitates Pavlovian extinction learning of fear and drug cues. Furthermore, DCS-augmented exposure therapy seems to be beneficial in various anxiety disorders, while the supposed working mechanism of DCS during human appetitive or aversive extinction learning is still not confirmed.
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d-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors.
Female participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS-) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation).

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It is well established that D-cycloserine (DCS), a partial agonist of the NMDA receptor glycine site, enhances learning and memory processes. Although the effects of DCS have been especially elucidated in the extinction and reconsolidation of aversive behavioral paradigms or drug-related behaviors, they have not been clearly determined in appetitive tasks using natural reinforcers. The current study examined the effects of pre-retrieval intra-basolateral amygdala (BLA) infusions of DCS on the extinction and reconsolidation of an appetitive odor discrimination task.

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The effectiveness of D-cycloserine (DCS), an N-methyl-D-aspartate glutamate receptor partial agonist, and valproic acid (VPA), a histone deacetylase inhibitor, in facilitating the extinction of fear-conditioned memory has been explored in humans and animals. Here, we confirmed whether DCS (100 mg) and VPA (400 mg) act in off-line learning processes during sleep or waking, for further clinical application to anxiety disorders and posttraumatic stress disorder (PTSD). We performed a randomized, blind, placebo-controlled clinical trial in 90 healthy adults.

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d-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl-d-aspartate (NMDA) receptor complex, has been shown to facilitate the extinction and prevent the relapse of cocaine-induced conditioned place preference (CPP) when administered before or after each extinction trail. However, some studies have suggested that DCS does not influence or even enhance relapse of seeking behavior on cocaine self-administration (SA) in rats or cocaine-dependent individuals undergoing clinical exposure treatment. Furthermore, there are no reports on the effects of DCS and the extinction of morphine-conditioned behaviors in mice.

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