Search

MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, combined with psychotherapy has demonstrated efficacy for the treatment of chronic posttraumatic stress disorder (PTSD) patients. This controlled prospective study aimed to assess the bio-behavioral underpinnings of MDMA in a translational model of PTSD. Rats exposed to predator-scent stress (PSS) were subjected to a trauma-cue at day 7 shortly after single-dose MDMA injection (5 mg/kg). The elevated plus maze and acoustic startle response tests were assessed on day 14 and served for classification into behavioral response groups. Freezing response to a further trauma-reminder was assessed on Day 15. The morphological characteristics of the dentate gyrus (DG) and basolateral amygdala (BLA) were subsequently examined. Hypothalamic-pituitary-adrenal axis and 5-hydroxytryptamine involvement were evaluated using: (1) corticosterone measurements at 2 h and 4 h after MDMA treatment, (2) Lewis strain rats with blunted HPA-response and (3) pharmacological receptor-blockade. MDMA treatment was effective in attenuating stress behavioral responses only when paired with memory reactivation by a trauma-cue. The effects of the treatment on behavior were associated with a commensurate normalization of the dendritic cytoarchitecture of DG and BLA neurons. Pretreatment with RU486, Ketanserin, or Pindolol prevented the above improvement in anxiety-like behavioral responses. MDMA treatment paired with memory reactivation reduced the prevalence rate of PTSD-phenotype 14 days later and normalized the cytoarchitecture changes induced by PSS (in dendritic complexities) compared to saline control. MDMA treatment paired with a trauma-cue may modify or update the original traumatic memory trace through reconsolidation processes. These anxiolytic-like effects seem to involve the HPA axis and 5-HT systems., (© 2022. The Author(s).)

The menstrual cycle is characterized partially by fluctuations of the ovarian hormones estradiol (E2) and progesterone (P4), which are implicated in the regulation of cognition. Research on attention in the different stages of the menstrual cycle is eclectic with discrepancies in attention definitions, and the three attentional networks (alerting, orienting and executive) and their interaction were not explored during the menstrual cycle. In the current study, we used the ANT-I (attentional network test - interactions) to examine naturally cycling women (NC) and women using oral contraceptives (OC). We tested their performance at two time points that fit, in natural cycles, the follicular phase and the luteal phase. We found no differences in performance between the two time points (day 4 / day 18) for the OC group: the response pattern replicated known ANT-I findings. However, the NC group showed differences between the two time points. In the follicular phase, responses replicated known ANT-I results, but in the luteal phase, alertness did not interact with executive and orienting networks, resulting in a larger congruency effect (executive network) when attention was not oriented to the target in alerting and no alerting conditions. Results-driven exploratory regression analysis of E2 and P4 suggested that change in P4 from the follicular phase/day 4 to the luteal phase/day 18 was a mediator for the alerting effect found between groups. In conclusion, the alerting state, found with or without alertness manipulation, suggests that there is a progesterone-mediated activation of the alerting system during the luteal phase., (Copyright © 2022 Elsevier B.V. All rights reserved.)