PMID- 36388136
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221119
IS  - 2666-3546 (Electronic)
IS  - 2666-3546 (Linking)
VI  - 26
DP  - 2022 Dec
TI  - MDMA administration attenuates hippocampal IL-beta immunoreactivity and subsequent 
      stress-enhanced fear learning: An animal model of PTSD.
PG  - 100542
LID - 10.1016/j.bbih.2022.100542 [doi]
LID - 100542
AB  - Post-traumatic stress disorder (PTSD) is a devastating disorder that involves 
      maladaptive changes in immune status. Using the stress-enhanced fear learning 
      (SEFL) paradigm, an animal model of PTSD, our laboratory has demonstrated 
      increased pro-inflammatory cytokine immunoreactivity in the hippocampus following 
      severe stress. Recent clinical trials have demonstrated 
      3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy as an effective 
      novel treatment for PTSD. Interestingly, MDMA has been shown to have an 
      immunosuppressive effect in both pre-clinical and clinical studies. Therefore, we 
      predict MDMA administration may attenuate SEFL, in part, due to an 
      immunosuppressive mechanism. The current studies test the hypothesis that MDMA is 
      capable of attenuating SEFL and inducing alterations in expression of TNF-alpha, 
      IL-1beta, glial fibrillary acidic protein (GFAP), an astrocyte specific marker, and 
      ionized calcium-binding adapter molecule -1 (IBA-1), a microglial specific 
      marker, in the dorsal hippocampus (DH) following a severe stressor in male 
      animals. To this end, experiment 1 determined the effect of MDMA administration 
      0, 24, and 48 h following a severe foot shock stressor on SEFL. We identified 
      that MDMA administration significantly attenuated SEFL. Subsequently, experiment 
      2 determined the effect of MDMA administration following a severe stressor on the 
      expression of TNF-alpha, IL-1beta, GFAP, and IBA-1 in the DH. We found that MDMA 
      administration significantly attenuated stress-induced IL-1beta and stress-reduced 
      IBA-1 but had no effect on TNF-alpha or GFAP. Overall, these results support the 
      hypothesis that MDMA blocks SEFL through an immunosuppressive mechanism and 
      supports the use of MDMA as a potential therapeutic agent for those experiencing 
      this disorder. Together, these experiments are the first to examine the effect of 
      MDMA in the SEFL model and these data contribute significantly towards the 
      clinical PTSD findings.
CI  - (c) 2022 The Authors.
FAU - Parekh, Shveta V
AU  - Parekh SV
AD  - Department of Psychology and Neuroscience, University of North Carolina at Chapel 
      Hill, CB#3720, Chapel Hill, NC, 27599-3270, USA.
FAU - Adams, Lydia O
AU  - Adams LO
AD  - Department of Psychology and Neuroscience, University of North Carolina at Chapel 
      Hill, CB#3720, Chapel Hill, NC, 27599-3270, USA.
FAU - Barkell, Gillian A
AU  - Barkell GA
AD  - Department of Psychology and Neuroscience, University of North Carolina at Chapel 
      Hill, CB#3720, Chapel Hill, NC, 27599-3270, USA.
FAU - Lysle, Donald T
AU  - Lysle DT
AD  - Department of Psychology and Neuroscience, University of North Carolina at Chapel 
      Hill, CB#3720, Chapel Hill, NC, 27599-3270, USA.
LA  - eng
PT  - Journal Article
DEP - 20221029
PL  - United States
TA  - Brain Behav Immun Health
JT  - Brain, behavior, & immunity - health
JID - 101759062
PMC - PMC9640320
OTO - NOTNLM
OT  - 3,4-Methylenedioxymethamphetamine (MDMA)
OT  - Astrocyte
OT  - Cytokine
OT  - Hippocampus
OT  - Interleukin-1beta (IL-beta)
OT  - Microglia
OT  - Post-traumatic stress disorder (PTSD)
OT  - Stress-enhanced fear learning (SEFL)
OT  - Tumor necrosis factor-alpha (TNF-alpha)
COIS- The authors declare no conflict of interests.
EDAT- 2022/11/18 06:00
MHDA- 2022/11/18 06:01
PMCR- 2022/10/29
CRDT- 2022/11/17 12:07
PHST- 2022/08/28 00:00 [received]
PHST- 2022/10/07 00:00 [revised]
PHST- 2022/10/23 00:00 [accepted]
PHST- 2022/11/17 12:07 [entrez]
PHST- 2022/11/18 06:00 [pubmed]
PHST- 2022/11/18 06:01 [medline]
PHST- 2022/10/29 00:00 [pmc-release]
AID - S2666-3546(22)00132-6 [pii]
AID - 100542 [pii]
AID - 10.1016/j.bbih.2022.100542 [doi]
PST - epublish
SO  - Brain Behav Immun Health. 2022 Oct 29;26:100542. doi: 10.1016/j.bbih.2022.100542. 
      eCollection 2022 Dec.