Abstract
This study tested whether l-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg l-DOPA/carbidopa (n = 28), or 200/50 mg l-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of l-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that l-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.
Highlights
Posttraumatic stress disorder (PTSD) is associated with marked impairment[1]
Across both skin conductance responding (SCR), neural network, and voxelwise indices of fear recall, the most robust association with L-DOPA was decreased fear responding following reinstatement compared to placebo
The SCR in these data did not provide clear evidence of fear recall in the acquisition context, such that there was no overall increase to the CS+ compared to CS−
Summary
Posttraumatic stress disorder (PTSD) is associated with marked impairment[1]. Exposure-based therapy is among the best supported interventions for PTSD2, yet remission rates are typically only 50–60%3,4. The role of dopaminergic signaling during the post-fear extinction consolidation window has not been investigated in PTSD, despite a growing body of data implicating dopamine as a critical mechanism underlying fear extinction learning, consolidation, and subsequent recall[9,10,11,12,13,14,15]. Animal models have demonstrated that dopamine agonists delivered during or following fear extinction learning[9,12,13] decrease subsequent fear responding. Chemogenetic studies further suggest a key role of dopaminergic neurons projecting to the striatum in mediating fear extinction learning[10,11,16]. Studies among healthy men demonstrate that the dopamine precursor L-DOPA delivered following extinction learning reduced subsequent context renewal[9] and improved extinction recall[17], possibly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
