Editing Fear (section)

==Research==
In order to improve our understanding of the neural and behavioral mechanisms of adaptive and maladaptive fear, investigators use a variety of translational animal models.<ref>{{cite journal | vauthors = Raber J, Arzy S, Bertolus JB, Depue B, Haas HE, Hofmann SG, Kangas M, Kensinger E, Lowry CA, Marusak HA, Minnier J, Mouly AM, Mühlberger A, Norrholm SD, Peltonen K, Pinna G, Rabinak C, Shiban Y, Soreq H, van der Kooij MA, Lowe L, Weingast LT, Yamashita P, Boutros SW | display-authors = 6 | title = Current understanding of fear learning and memory in humans and animal models and the value of a linguistic approach for analyzing fear learning and memory in humans | journal = Neuroscience and Biobehavioral Reviews | volume = 105 | pages = 136–177 | date = October 2019 | pmid = 30970272 | doi = 10.1016/j.neubiorev.2019.03.015 | s2cid = 102353770 | doi-access = free }}</ref> These models are particularly important for research that would be too invasive for human studies. Rodents such as mice and rats are common animal models, but other species are used. Certain aspects of fear research still requires more research such as sex, gender, and age differences.

===Models===
{{See also|Model organism}}

These animal models include, but are not limited to, fear conditioning, predator-based psycho[[social stress]], single prolonged stress, chronic stress models, inescapable foot/tail shocks, immobilization or restraint, and stress enhanced fear learning. While the stress and fear paradigms differ between the models, they tend to involve aspects such as acquisition, generalization, extinction, cognitive regulation, and reconsolidation.<ref>{{cite book | vauthors = Hartley CA, Phelps EA |chapter=Fear Models in Animals and Humans|date=2013 |title=Pediatric Anxiety Disorders|pages=3–21| veditors = Vasa RA, Roy AK |place=New York|publisher=Springer New York|language=en|doi=10.1007/978-1-4614-6599-7_1|isbn=978-1-4614-6598-0}}</ref><ref>{{cite journal | vauthors = Luchkina NV, Bolshakov VY | title = Mechanisms of fear learning and extinction: synaptic plasticity-fear memory connection | journal = Psychopharmacology | volume = 236 | issue = 1 | pages = 163–182 | date = January 2019 | pmid = 30415278 | pmc = 6374177 | doi = 10.1007/s00213-018-5104-4 }}</ref>

==== Pavlovian ====
{{Main|Fear conditioning}}

Fear conditioning, also known as Pavlovian or classical conditioning, is a process of learning that involves pairing a neutral stimulus with an unconditional stimulus (US).<ref>{{cite journal | vauthors = Maren S | title = Neurobiology of Pavlovian fear conditioning | journal = Annual Review of Neuroscience | volume = 24 | pages = 897–931 | date = 2001 | issue = 1 | pmid = 11520922 | doi = 10.1146/annurev.neuro.24.1.897 | url = https://pubmed.ncbi.nlm.nih.gov/11520922 | hdl = 2027.42/61939 | hdl-access = free }}</ref> A neutral stimulus is something like a bell, tone, or room that does not elicit a response normally where a US is a stimulus that results in a natural or unconditioned response (UR) – in Pavlov's famous experiment the neutral stimulus is a bell and the US would be food with the dog's salvation being the UR. Pairing the neutral stimulus and the US results in the UR occurring not only with the US but also the neutral stimulus. When this occurs the neutral stimulus is referred to as the conditional stimulus (CS) and the response the conditional response (CR). In the fear conditioning model of Pavlovian conditioning the US is an aversive stimulus such as a shock, tone, or unpleasant odor.

==== Predator-based psychosocial stress ====
Predator-based psychosocial stress (PPS) involves a more naturalistic approach to fear learning.<ref name=":0">{{cite journal | vauthors = Richter-Levin G, Stork O, Schmidt MV | title = Animal models of PTSD: a challenge to be met | journal = Molecular Psychiatry | volume = 24 | issue = 8 | pages = 1135–1156 | date = August 2019 | pmid = 30816289 | pmc = 6756084 | doi = 10.1038/s41380-018-0272-5 }}</ref> Predators such as a cat, a snake, or urine from a fox or cat are used along with other stressors such as immobilization or restraint in order to generate instinctual fear responses.<ref>{{cite journal | vauthors = Zoladz PR, Eisenmann ED, Rose RM, Kohls BA, Johnson BL, Robinson KL, Heikkila ME, Mucher KE, Huntley MR | display-authors = 6 | title = Predator-based psychosocial stress model of PTSD differentially influences voluntary ethanol consumption depending on methodology | journal = Alcohol | volume = 70 | pages = 33–41 | date = August 2018 | pmid = 29775837 | doi = 10.1016/j.alcohol.2018.01.004 | s2cid = 21734755 | url = https://linkinghub.elsevier.com/retrieve/pii/S0741832917308297 }}</ref>

==== Chronic stress models ====
Chronic stress models include chronic variable stress, chronic social defeat, and chronic mild stress.<ref name=":0" /><ref>{{cite journal | vauthors = Willner P | title = The chronic mild stress (CMS) model of depression: History, evaluation and usage | journal = Neurobiology of Stress | volume = 6 | pages = 78–93 | date = February 2017 | pmid = 28229111 | pmc = 5314424 | doi = 10.1016/j.ynstr.2016.08.002 }}</ref> These models are often used to study how long-term or prolonged stress/pain can alter fear learning and disorders.<ref name=":0" /><ref>{{cite journal | vauthors = Abdallah CG, Geha P | title = Chronic Pain and Chronic Stress: Two Sides of the Same Coin? | journal = Chronic Stress | volume = 1 | date = February 2017 | pmid = 28795169 | pmc = 5546756 | doi = 10.1177/2470547017704763 }}</ref>

==== Single prolonged stress ====
Single prolonged stress (SPS) is a fear model that is often used to study PTSD.<ref>{{cite journal | vauthors = Lisieski MJ, Eagle AL, Conti AC, Liberzon I, Perrine SA | title = Single-Prolonged Stress: A Review of Two Decades of Progress in a Rodent Model of Post-traumatic Stress Disorder | journal = Frontiers in Psychiatry | volume = 9 | page = 196 | date = 2018-05-15 | pmid = 29867615 | pmc = 5962709 | doi = 10.3389/fpsyt.2018.00196 | doi-access = free }}</ref><ref name=":1">{{cite journal | vauthors = Souza RR, Noble LJ, McIntyre CK | title = Using the Single Prolonged Stress Model to Examine the Pathophysiology of PTSD | journal = Frontiers in Pharmacology | volume = 8 | page = 615 | date = 2017-09-11 | pmid = 28955225 | pmc = 5600994 | doi = 10.3389/fphar.2017.00615 | doi-access = free }}</ref> Its paradigm involves multiple stressors such as immobilization, a force swim, and exposure to ether delivered concurrently to the subject.<ref name=":1" /> This is used to study non-naturalistic, uncontrollable situations that can cause a maladaptive fear responses that is seen in a lot of anxiety and traumatic based disorders.

==== Stress enhanced fear learning ====
Stress enhanced fear learning (SEFL) like SPS is often used to study the maladaptive fear learning involved in PTSD and other traumatic based disorders.<ref name=":0" /><ref>{{cite journal | vauthors = Rau V, DeCola JP, Fanselow MS | title = Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder | journal = Neuroscience and Biobehavioral Reviews | volume = 29 | issue = 8 | pages = 1207–1223 | date = January 2005 | pmid = 16095698 | doi = 10.1016/j.neubiorev.2005.04.010 | url = https://linkinghub.elsevier.com/retrieve/pii/S0149763405000606 | s2cid = 5896548 }}</ref> SEFL involves a single extreme stressor such as a large number of footshocks simulating a single traumatic stressor that somehow enhances and alters future fear learning.<ref name=":0" /><ref>{{cite journal | vauthors = Rajbhandari AK, Gonzalez ST, Fanselow MS | title = Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder | journal = Journal of Visualized Experiments | issue = 140 | page= 58306 | date = October 2018 | pmid = 30371665 | pmc = 6235522 | doi = 10.3791/58306 | url = https://www.jove.com/video/58306/stress-enhanced-fear-learning-robust-rodent-model-post-traumatic }}</ref><ref>{{cite journal | vauthors = Rau V, Fanselow MS | title = Exposure to a stressor produces a long lasting enhancement of fear learning in rats | journal = Stress | volume = 12 | issue = 2 | pages = 125–133 | date = March 2009 | pmid = 18609302 | doi = 10.1080/10253890802137320 | s2cid = 15453890 | doi-access = free }}</ref>