AbstractDespite advances in the treatment of fear-, anxiety- and trauma-related disorders, a considerable proportion of patients shows only partial long-term therapeutic benefit with existing treatments. A promising option in improving therapy is speeding up and boosting the effect of exposure-based therapy (EBT) by pharmacological interventions. Here, we will discuss select examples of novel concepts in augmenting fear extinction, the central mechanisms of EBT. Based on accumulating knowledge from animal and human studies concerning the neurocircuitries and neurobiological mechanisms underlying successful fear extinction, diverse potential pharmacological targets have been identified to optimize the efficacy of fear extinction. We focus here on selected examples of these targets and present translational evidence for strengthening fear inhibitory learning by using L-DOPA and D-cycloserine. Furthermore, the potential of HDAC inhibitors and microRNAs (e. g. miR-144) as epigenetic targets, as well as neuropeptide S as a model substance with combined acute anxiolytic and extinction-facilitating properties are discussed. The presented mechanisms represent promising novel strategies that may be useful in the future for augmenting the efficacy and improving the acceptance of EBT in the treatment of anxiety disorders, although further work remains to be done in characterising the underlying modes of action and safety aspects.
Neuroforum – de Gruyter
Published: Nov 27, 2017
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