Combined administration of D-cycloserine (DCS) and MK-801 disrupts threat memory reconsolidation in mice and reduces pERK-expressing neurons in the lateral amygdala — The Association Specialists
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Combined administration of D-cycloserine (DCS) and MK-801 disrupts threat memory reconsolidation in mice and reduces pERK-expressing neurons in the lateral amygdala (21523)

sayed koushik ahamed 1 2 , Sanket Raut 2 3 4 , Fionnghuala James 2 5 , Vanni Caruso 6 , Sukhwinder S. Sohal 7 , Luke Johnson 2 8 9
  1. Pharmacy and pharmacology, PhD Candidates, Hobart, TASMANIA, Australia
  2. School of Psychological Sciences , University of Tasmania, LAUNCESTON, Australia
  3. School of Medicine, University of Queensland, , Research Fellow , Brisbane, Queensland, Australia
  4. Gallipoli Medical Research , Research Fellow, Brisbane, Qu
  5. Pharmacy and pharmacology, PhD candidates, Hobart, Tasmania, Australia
  6. School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TASMANIA, Australia
  7. Health Sciences, University of Tasmania, LAUNCESTON, TAS, Australia
  8. School of Medicine, , University of Queensland, Brisbane, Queensland, Australia
  9. Center for the Study of Traumatic Stress, USU School of Medicine, Bethesda, MD, USA

Background and Objective: Post-traumatic stress disorder (PTSD) is characterized by persistent threat-related memories with limited effective treatment options. The N-methyl-D-aspartate (NMDA) receptor dependent extracellular signal-regulated kinase (ERK) pathway in the lateral amygdala (LA) is necessary for synaptic plasticity and memory processes, including threat memory consolidation and reconsolidation. Reconsolidation requires memories to be brought into a labile state. Disruption of these memories during the reconsolidation window has been proposed as a therapeutic strategy for PTSD. We investigated the effect of the NMDA receptor agonist D-cycloserine (DCS) and antagonist MK801 on threat memory reconsolidation in male C57BL/6 mice.

Method: Using auditory threat conditioning, DCS or a vehicle was administered one hour before memory reactivation to facilitate labialisation of a recalled threat memory, followed by MK-801 or a vehicle after reactivation to disrupt the memory. Experimental groups included vehicle, DCS 15 mg/kg, MK-801 0.06 mg/kg, and MK-801 0.12 mg/kg alone and combined. The effect on phosphorylated ERK (pERK) expressing neurons was analysed using neuron counting and topographical mapping in the lateral amygdala (LA).

Results: MK-801 alone (P = 0.0421 and 0.0228) and in combination with DCS (P = 0.0040 and 0.0007) significantly reduced the number of pERK-expressing neurons in the LA. Freezing behaviour was reduced by high dose MK801 when combined with DCS.

Conclusion: These findings suggest that DCS and MK-801 together effectively disrupt pERK expressing neurons and disrupt fear memory reconsolidation, offering new MDMA receptor-based treatment strategies for PTSD.