Effects of augmentation agents on emotional memory consolidation and subliminal cue exposure to fear-relavent stimuli
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Seminal research demonstrated that both systemic administration and direct intra-amygdala infusions of d-cycloserine (DCS) in rats enhances extinction learning of fear. This research catalyzed further investigation of cognitive enhancers in preclinical and clinical populations, offering support for a beneficial effect of these agents on exposure-based learning. However, the exact mechanisms of action involved remain unclear. The two studies presented in this paper explore potential mechanisms of action of cognitive enhancers in memory consolidation and extinction learning. Study 1 examined the effect of DCS and cortisone, another cognitive enhancer, on emotional memory consolidation in a nonclinical sample to investigate the effect of these augmentation agents on emotional recall. Men with no current psychological disorder participated in a two-day study involving randomization to one of four groups: DCS, cortisone, DCS plus cortisone, and placebo. All participants completed an emotional memory task on day 1 and completed a recall test on day 2. Participants receiving DCS demonstrated differential memory for negative stimuli, in that memory for negative items was significantly worse for individuals taking a single dose of DCS. Study 2 examined the effect of DCS in a two-day design on extinction learning through a subliminal cue paradigm that activates the amygdala without conscious awareness. Participants that met criteria for a specific phobia of spiders (excluding the daily interference criteria) were randomized to receive placebo or DCS on day 1. All participants completed a subliminal cue exposure task to spiders on day 1. Results demonstrated that individuals in the DCS group had significantly greater reductions in disgust on day 2 as compared to the placebo group. However, there was no significant reduction in fear between the groups. Analyses were then conducted on the portion of the sample that did not report seeing spiders on the subliminal task, and the same pattern of results was demonstrated with disgust, while fear approached significance at a trend level. These findings have implications for clarifying mechanisms of action with respect to cognitive enhancers, which may ultimately help reduce time patients spend in exposure-based treatments.
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