Effects of HDAC inhibitors on spatial memory and memory extinction in SPS-induced PTSD rats

Ahmad Mohammadi-Farani , Ali Pourmotabbed, Yazdan Ardeshirizadeh

Abstract


Background and purpose: Neurobiological changes in memory processes seem to play a role in the pathophysiology of post-traumatic stress disorder (PTSD). Memory itself is influenced by PTSD, too. Histone deacetylase inhibitors (HDAIs) have shown promising results in the extinction of fear-related memories in animals and hence they seem to be important for the treatment of PTSD. Data are scarce about the effect of HDAIs in spatial memory formation/extinction in PTSD models. The main goal of the present work is to find the effect of sodium butyrate (NaBu), as an HDAI, on spatial memory and spatial memory extinction in rats exposed to single prolonged stress procedure (SPS).

Experimental approach: Different doses of NaBu were administered subcutaneously for 7 days in different groups of rats after SPS procedure. Learning, memory, and extinction of memory were evaluated in the Morris water maze test of spatial memory in 6 consecutive days.

Findings / Results: The results show that NaBu (0.5 mg/kg) alleviates impaired learning and memory in SPS rats. It also facilitates the extinction of newly formed memory in the animals.

Conclusion and implications: Our data suggest that the administration of HDAIs after a traumatic experience can prevent the aversive effects of SPS on spatial memory. It also reinforces the notion that extinction of spatial memory involves the same or similar brain circuitry that is involved in the extinction of fear memories in PTSD patients.

 

 


Keywords


Extinction; Histone deacetylase inhibitors; PTSD; Spatial memory.

Full Text:

PDF

References


Miao XR, Chen QB, Wei K, Tao KM, Lu ZJ. Posttraumatic stress disorder: from diagnosis to prevention. Mil Med Res. 2018;5(1):32-38.

DOI: 10.1186/s40779-018-0179-0.

Abdallah CG, Southwick SM, Krystal JH. Neurobiology of posttraumatic stress disorder (PTSD): a path from novel pathophysiology to innovative therapeutics. Neurosci Lett. 2017;649:130-132.

DOI: 10.1016/j.neulet.2017.04.046.

Cain CK, Maynard GD, Kehne JH. Targeting memory processes with drugs to prevent or cure PTSD. Expert Opin Investig Drugs. 2012;21(9):1323-1350.

DOI: 10.1517/13543784.2012.704020.

Bouton ME, Westbrook RF, Corcoran KA, Maren S. Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry. 2006;60(4):352-360.

DOI: 10.1016/j.biopsych.2005.12.015.

Harvey BH, Naciti C, Brand L, Stein DJ. Endocrine, cognitive and hippocampal/cortical 5HT 1A/2A receptor changes evoked by a time-dependent sensitisation (TDS) stress model in rats. Brain Res. 2003;983(1-2):97-107.

DOI: 10.1016/s0006-8993(03)03033-6.

Kohda K, Harada K, Kato K, Hoshino A, Motohashi J, Yamaji T, et al. Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model. Neuroscience. 2007;148(1):22-33.

DOI: 10.1016/j.neuroscience.2007.05.041.

Tempesta D, Mazza M, Iaria G, De Gennaro L, Ferrara M. A specific deficit in spatial memory acquisition in post-traumatic stress disorder and the role of sleep in its consolidation. Hippocampus. 2012;22(5):1154-1163.

DOI: 10.1002/hipo.20961.

Smith KV, Burgess N, Brewin CR, King JA. Impaired allocentric spatial processing in posttraumatic stress disorder. Neurobiol Learn Mem. 2015;119:69-76.

DOI: 10.1016/j.nlm.2015.01.007.

Miller JK, McDougall S, Thomas S, Wiener JM. Impairment in active navigation from trauma and post-traumatic stress disorder. Neurobiol Learn Mem. 2017;140:114-123.

DOI: 10.1016/j.nlm.2017.02.019.

Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLoS One. 2011;6(5):e19958,1-13.

DOI: 10.1371/journal.pone.0019958.

Whittle N, Singewald N. HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: where do we stand? Biochem Soc Trans. 2014;42(2):569-581.

DOI: 10.1042/BST20130233.

Stafford JM, Raybuck JD, Ryabinin AE, Lattal KM. Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biol Psychiatry. 2012;72(1):25-33.

DOI: 10.1016/j.biopsych.2011.12.012.

Whittle N, Schmuckermair C, Gunduz Cinar O, Hauschild M, Ferraguti F, Holmes A, et al. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model. Neuropharmacology. 2013;64:414-423.

DOI: 10.1016/j.neuropharm.2012.06.001.

Lattal KM, Barrett RM, Wood MA. Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci. 2007;121(5):1125-1131.

DOI: 10.1037/0735-7044.121.5.1125.

Itzhak Y, Anderson KL, Kelley JB, Petkov M. Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice. Neurobiol Learn Mem. 2012;97(4):409-417.

DOI: 10.1016/j.nlm.2012.03.005.

Liberzon I, Krstov M, Young EA. Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrino. 1997;22(6):443-453.

DOI: 10.1016/s0306-4530(97)00044-9.

Mohammad Alizadeh MA, Abrari K, Lashkar Blouki T, Ghorbanian MT, Jadidi M. Pulsed electromagnetic field attenuated PTSD-induced failure of conditioned fear extinction. Iran J Basic Med Sci. 2019;22(6):650-659.

DOI: 10.22038/ijbms.2019.32576.7797.

Mohammadi-Farani A, Haghighi A, Ghazvineh M. Effects of long term administration of testosterone and estradiol on spatial memory in rats. Res Pharm Sci. 2015;10(5):407-418.

Mendez-Couz M, Conejo NM, Vallejo G, Arias JL. Spatial memory extinction: a c-Fos protein mapping study. Behav Brain Res. 2014;260:101-110.

DOI: 10.1016/j.bbr.2013.11.032.

Rossato JI, Bevilaqua LR, Medina JH, Izquierdo I, Cammarota M. Retrieval induces hippocampal-dependent reconsolidation of spatial memory. Learn Mem. 2006;13(4):431-440.

DOI: 10.1101/lm.315206.

Diagnostic and statistical manual of mental disorders: DSM-5. Fifth edition.

DOI: 10.1176/appi.books.9780890425596.

Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Nazeer A, et al. MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry. 2003;160(5):924-932.

DOI: 10.1176/appi.ajp.160.5.924.

Elzinga BM, Bremner JD. Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)? J Affect Disord. 2002;70(1):1-17.

DOI: 10.1016/s0165-0327(01)00351-2.

Fenster RJ, Lebois LAM, Ressler KJ, Suh J. Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man. Nat Rev Neurosci. 2018;19(9):535-551.

DOI: 10.1038/s41583-018-0039-7.

Bremner JD, Scott TM, Delaney RC, Southwick SM, Mason JW, Johnson DR, et al. Deficits in short-term memory in posttraumatic stress disorder. Am J Psychiatry. 1993;150(7):1015-1019.

DOI: 10.1176/ajp.150.7.1015.

Bremner JD, Vythilingam M, Vermetten E, Southwick SM, McGlashan T, Staib LH, et al. Neural correlates of declarative memory for emotionally valenced words in women with posttraumatic stress disorder related to early childhood sexual abuse. Biol Psychiatry. 2003;53(10):879-889.

DOI: 10.1016/s0006-3223(02)01891-7.

Diamond DM, Fleshner M, Ingersoll N, Rose GM. Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behav Neurosci. 1996;110(4):661-672.

DOI: 10.1037//0735-7044.110.4.661.

Luine V, Villegas M, Martinez C, McEwen BS. Repeated stress causes reversible impairments of spatial memory performance. Brain Res. 1994;639(1):167-170.

DOI: 10.1016/0006-8993(94)91778-7.

Goodman J, McIntyre CK. Impaired spatial memory and enhanced habit memory in a rat model of post-traumatic stress disorder. Front Pharmacol. 2017;8:663-670.

DOI: 10.3389/fphar.2017.00663.

Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem. 2004;279(39):40545-40559.

DOI: 10.1074/jbc.M402229200.

Koshibu K, Graff J, Beullens M, Heitz FD, Berchtold D, Russig H, et al. Protein phosphatase 1 regulates the histone code for long-term memory. J Neurosci. 2009;29(41):13079-13089.

DOI: 10.1523/JNEUROSCI.3610-09.2009.

Milad MR, Rauch SL, Pitman RK, Quirk GJ. Fear extinction in rats: implications for human brain imaging and anxiety disorders. Biol Psychol. 2006;73(1):61-71.

DOI: 10.1016/j.biopsycho.2006.01.008.

Quirk GJ, Garcia R, Gonzalez-Lima F. Prefrontal mechanisms in extinction of conditioned fear. Biol Psychiatry. 2006;60(4):337-343.

DOI: 10.1016/j.biopsych.2006.03.010.

Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research-past, present, and future. Biol Psychiatry. 2006;60(4):376-382.

DOI: 10.1016/j.biopsych.2006.06.004.

Singewald N, Holmes A. Rodent models of impaired fear extinction. Psychopharmacology (Berl). 2019;236(1):21-32.

DOI: 10.1007/s00213-018-5054-x.

Prados J, Sansa J, Artigas AA. Partial reinforcement effects on learning and extinction of place preferences in the water maze. Learn Behav. 2008;36(4):311-318.

DOI: 10.3758/LB.36.4.311.

Huston JP, Schulz D, Topic B. Toward an animal model of extinction-induced despair: focus on aging and physiological indices. J Neural Transm (Vienna). 2009;116(8):1029-1036.

DOI: 10.1007/s00702-009-0210-4.

Knox D, George SA, Fitzpatrick CJ, Rabinak CA, Maren S, Liberzon I. Single prolonged stress disrupts retention of extinguished fear in rats. Learn Mem. 2012;19(2):43-49.

DOI: 10.1101/lm.024356.111.

Ledgerwood L, Richardson R, Cranney J. D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement. Behav Neurosci. 2004;118(3):505-513.

DOI: 10.1037/0735-7044.118.3.505.

Lin CC, Tung CS, Lin PH, Huang CL, Liu YP. Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder. Eur Neuropsychopharmacol. 2016;26(9):1484-1495.

DOI: 10.1016/j.euroneuro.2016.06.004.

Souza RR, Robertson NM, Pruitt DT, Gonzales PA, Hays SA, Rennaker RL, et al. Vagus nerve stimulation reverses the extinction impairments in a model of PTSD with prolonged and repeated trauma. Stress. 2019;22(4):509-520.

DOI: 10.1080/10253890.2019.1602604.

Yamamoto S, Morinobu S, Iwamoto Y, Ueda Y, Takei S, Fujita Y, et al. Alterations in the hippocampal glycinergic system in an animal model of posttraumatic stress disorder. J Psychiatr Res. 2010;44(15):1069-1074.

DOI: 10.1016/j.jpsychires.2010.03.013.

Smith NB, Doran JM, Sippel LM, Harpaz-Rotem I. Fear extinction and memory reconsolidation as critical components in behavioral treatment for posttraumatic stress disorder and potential augmentation of these processes. Neurosci Lett. 2017;649:170-175.

DOI: 10.1016/j.neulet.2017.01.006.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.