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Physiology & Behavior Nov 1993In Experiment 1, Wistar-Kyoto (WKY), Wistar, and Fischer-344 (F-344) rats were tested on two passive-avoidance tasks: a platform step-down task and a one-way avoidance... (Comparative Study)
Comparative Study
In Experiment 1, Wistar-Kyoto (WKY), Wistar, and Fischer-344 (F-344) rats were tested on two passive-avoidance tasks: a platform step-down task and a one-way avoidance task. Wistars had shorter response latency scores in the step-down task, whereas F-344 rats had shorter scores in the one-way task. A subsequent ulcerogenic water-restraint stress produced significantly fewer ulcers in Wistar rats as compared to WKY and F-344 rats. In Experiment 2, rearings, grooming, ambulation, defecation, and response ambivalence behaviors were recorded in the one-way avoidance task in addition to response latency. WKY rats defecated more and produced lower scores on the three activity measures as compared to Wistar and F-344 rats. Response latency and ambivalence scores were higher for WKY rats. The subsequent ulcerogenic procedure also produced more ulcers in WKY rats. These data verify the ulcer susceptibility of WKY rats and underscore the assertion that their predominant stress coping behaviors are immobility and freezing. High ambivalence scores in WKY rats suggest behavioral inhibition, which is readily elicited by stressors. These behaviors resemble depressive behavior and suggest that WKY rat may be a useful animal model of depression.
Topics: Animals; Arousal; Avoidance Learning; Fear; Male; Psychophysiology; Rats; Rats, Inbred F344; Rats, Inbred WKY; Rats, Wistar; Reaction Time; Species Specificity; Stomach Ulcer; Stress, Psychological
PubMed: 8248372
DOI: 10.1016/0031-9384(93)90291-m -
Molecular Psychiatry Feb 2020The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains...
The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.
Topics: Animals; Anxiety Disorders; Avoidance Learning; Brain; Cell Line; Corpus Striatum; Female; Gray Matter; Habits; Inhibition, Psychological; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Optogenetics; Receptors, Dopamine D2; Stereotypic Movement Disorder
PubMed: 29695836
DOI: 10.1038/s41380-018-0051-3 -
Current Biology : CB Mar 2014Animal models of human anxiety often invoke a conflict between approach and avoidance. In these, a key behavioral assay comprises passive avoidance of potential threat...
Animal models of human anxiety often invoke a conflict between approach and avoidance. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus. Efforts to translate these approaches to clinical contexts are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.
Topics: Adult; Avoidance Learning; Conflict, Psychological; Defense Mechanisms; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nontherapeutic Human Experimentation; Video Games
PubMed: 24560572
DOI: 10.1016/j.cub.2014.01.046 -
Journal of Visualized Experiments : JoVE Oct 2021This protocol describes a new paradigm for analyzing aversive associative learning in adult flies (Drosophila melanogaster). The paradigm is analogous to passive...
This protocol describes a new paradigm for analyzing aversive associative learning in adult flies (Drosophila melanogaster). The paradigm is analogous to passive avoidance behavior in laboratory rodents in which animals learn to avoid a compartment where they have previously received an electric shock. The assay takes advantage of negative geotaxis in flies, which manifests as an urge to climb up when they are placed on a vertical surface. The setup consists of vertically oriented upper and lower compartments. On the first trial, a fly is placed into a lower compartment from where it usually exits within 3-15 s, and steps into the upper compartment where it receives an electric shock. During the second trial, 24 h later, the latency is significantly increased. At the same time, the number of shocks is decreased compared to the first trial, indicating that flies formed long-term memory about the upper compartment. The recordings of latencies and number of shocks could be performed with a tally counter and a stopwatch or with an Arduino-based simple device. To illustrate how the assay can be used, the passive avoidance behavior of D. melanogaster and D. simulans male and female were characterized here. Comparison of latencies and number of shocks revealed that both D. melanogaster and D. simulans flies efficiently learned the passive avoidance behavior. No statistical differences were observed between male and female flies. However, males were a little faster while entering the upper compartment on the first trial, while females received a slightly higher number of shocks in every retention trial. The Western diet (WD) significantly impaired learning and memory in male flies while flight exercise counterbalanced this effect. Taken together, the passive avoidance behavior in flies offers a simple and reproducible assay that could be used for studying basic mechanisms of learning and memory.
Topics: Animals; Avoidance Learning; Conditioning, Classical; Drosophila; Drosophila melanogaster; Female; Male
PubMed: 34723949
DOI: 10.3791/63163 -
Biological Psychiatry Jun 2019Investigations in the neocortex have revealed that the balance of excitatory and inhibitory synaptic transmission (E/I ratio) is important for proper information...
BACKGROUND
Investigations in the neocortex have revealed that the balance of excitatory and inhibitory synaptic transmission (E/I ratio) is important for proper information processing. The disturbance of this balance underlies many neuropsychiatric illnesses, including autism spectrum disorder and schizophrenia. However, little is known about the contribution of E/I balance to the functioning of subcortical brain regions, such as the lateral septum (LS), a structure that plays important roles in regulating anxiety-related behavior.
METHODS
We manipulated E/I balance in the mouse LS by localized conditional deletion of neuroligin-2, a postsynaptic cell adhesion protein located at gamma-aminobutyric acidergic synapses and important for inhibitory synaptic transmission. We then performed analyses of synaptic transmission in the LS, stress-induced expression of immediate early gene c-fos, and anxiety-related and depression-related behavior.
RESULTS
The absence of neuroligin-2 in the LS in the mature mouse brain resulted in postsynaptic impairment of inhibitory synaptic transmission. Importantly, the reduced inhibition and resulting E/I imbalance decreased the responsiveness of LS neurons to stress. Furthermore, this E/I imbalance in the LS was associated with impaired stress-induced activation of downstream hypothalamic nuclei and reduced avoidance behavior of the animals in the elevated plus maze.
CONCLUSIONS
Our results described the synaptic function of neuroligin-2 in the LS, uncovered a positive association between c-Fos-expressing neurons in the LS and downstream hypothalamic areas and avoidance behavior, and demonstrated that intact inhibitory synaptic transmission and proper E/I balance are required for the optimal functioning of this subcortical circuit.
Topics: Animals; Anxiety; Avoidance Learning; Cell Adhesion Molecules, Neuronal; Female; Male; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Septal Nuclei; Stress, Psychological; Synaptic Transmission
PubMed: 30878196
DOI: 10.1016/j.biopsych.2019.01.022 -
Trends in Cognitive Sciences Jul 2017Learning about potential threats is critical for survival. Learned fear responses are acquired either through direct experiences or indirectly through social... (Review)
Review
Learning about potential threats is critical for survival. Learned fear responses are acquired either through direct experiences or indirectly through social transmission. Social fear learning (SFL), also known as vicarious fear learning, is a paradigm successfully used for studying the transmission of threat information between individuals. Animal and human studies have begun to elucidate the behavioral, neural and molecular mechanisms of SFL. Recent research suggests that social learning mechanisms underlie a wide range of adaptive and maladaptive phenomena, from supporting flexible avoidance in dynamic environments to intergenerational transmission of trauma and anxiety disorders. This review discusses recent advances in SFL studies and their implications for basic, social and clinical sciences.
Topics: Animals; Anxiety Disorders; Association Learning; Avoidance Learning; Fear; Humans; Learning; Models, Animal; Models, Biological; Social Behavior; Social Learning
PubMed: 28545935
DOI: 10.1016/j.tics.2017.04.010 -
Psychopharmacology Aug 2019Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased... (Clinical Trial)
Clinical Trial
BACKGROUND
Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown.
METHODS
To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations.
RESULTS
Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms.
CONCLUSION
Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.
Topics: Affect; Avoidance Learning; Choice Behavior; Computer Simulation; Decision Making; Depression; Humans; Male; Models, Psychological; Photic Stimulation; Punishment; Reward; Young Adult
PubMed: 31254091
DOI: 10.1007/s00213-019-05299-9 -
The Journal of Pain Aug 2022Pain-related avoidance of movements that are actually safe (ie, overprotective behavior) plays a key role in chronic pain disability. Avoidance is reinforced through...
Pain-related avoidance of movements that are actually safe (ie, overprotective behavior) plays a key role in chronic pain disability. Avoidance is reinforced through operant learning: after learning that a certain movement elicits pain, movements that prevent pain are more likely to be performed. Proprioceptive accuracy importantly contributes to motor learning and memory. Interestingly, reduced accuracy has been documented in various chronic pain conditions, prompting the question whether this relates to avoidance becoming excessive. Using robotic arm-reaching movements, we tested the hypothesis that poor proprioceptive accuracy is associated with excessive pain-related avoidance in pain-free participants. Participants first performed a task to assess proprioceptive accuracy, followed by an operant avoidance training during which a pain stimulus was presented when they performed one movement trajectory, but not when they performed another trajectory. During a test phase, movements were no longer restricted to 2 trajectories, but participants were instructed to avoid pain. Unbeknownst to the participants, the pain stimulus was never presented during this phase. Results supported our hypothesis. Furthermore, exploratory analyses indicated a reduction in proprioceptive accuracy after avoidance learning, which was associated with excessive avoidance and higher trait fear of pain. PERSPECTIVE: This study is the first to show that poorer proprioceptive accuracy is associated with excessive pain-related avoidance. This finding is especially relevant for chronic pain conditions, as reduced accuracy has been documented in these populations, and points toward the need for research on training accuracy to tackle excessive avoidance.
Topics: Avoidance Learning; Chronic Pain; Humans; Movement; Proprioception
PubMed: 35341984
DOI: 10.1016/j.jpain.2022.03.233 -
The Journal of Pain Oct 2018Fear-avoidance models propose that pain-related fear may spur avoidance behavior leading to chronic pain disability. Pain-related fear elicits avoidance behavior, which... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Fear-avoidance models propose that pain-related fear may spur avoidance behavior leading to chronic pain disability. Pain-related fear elicits avoidance behavior, which is typically aimed at reducing fear. We hypothesized that engaging in avoidance may (paradoxically) increase rather than decrease pain-related fear (ie, bidirectionality hypothesis). In a between-subject design, participants (n = 64) were randomly assigned to the avoidance group or the control group. Avoidance group participants were led to believe they could avoid full exposure to a painful heat stimulus by pressing the stop button, whereas control group participants believed they were exposed to the full painful heat stimulus at all times. In reality and unknown to the participants, the intensity and duration of the heat stimulus was independent of the avoidance response, and was identical in both groups. During the test, the avoidance response (ie, pressing the stop button) was no longer available. As expected, pain-related fear levels were higher after avoiding the painful heat stimulus. Interestingly, in the avoidance group, pain-related fear increased after receiving instructions that avoidance would be possible, even before actually engaging in avoidance behavior. In the control group, no significant change was observed in pain-related fear throughout the experiment. The eyeblink startle measures did not corroborate this data pattern.
PERSPECTIVE
These observations provide partial support for the bidirectionality hypothesis between avoidance behavior and fear. These findings may have clinical implications and suggest that allowing avoidance behaviors during treatment may thwart fear reduction.
Topics: Adolescent; Adult; Avoidance Learning; Fear; Female; Humans; Male; Middle Aged; Pain; Young Adult
PubMed: 29777952
DOI: 10.1016/j.jpain.2018.05.003 -
PloS One 2015Avoidance behavior is a critical component of many psychiatric disorders, and as such, it is important to understand how avoidance behavior arises, and whether it can be...
Avoidance behavior is a critical component of many psychiatric disorders, and as such, it is important to understand how avoidance behavior arises, and whether it can be modified. In this study, we used empirical and computational methods to assess the role of informational feedback and ambiguous outcome in avoidance behavior. We adapted a computer-based probabilistic classification learning task, which includes positive, negative and no-feedback outcomes; the latter outcome is ambiguous as it might signal either a successful outcome (missed punishment) or a failure (missed reward). Prior work with this task suggested that most healthy subjects viewed the no-feedback outcome as strongly positive. Interestingly, in a later version of the classification task, when healthy subjects were allowed to opt out of (i.e. avoid) responding, some subjects ("avoiders") reliably avoided trials where there was a risk of punishment, but other subjects ("non-avoiders") never made any avoidance responses at all. One possible interpretation is that the "non-avoiders" valued the no-feedback outcome so positively on punishment-based trials that they had little incentive to avoid. Another possible interpretation is that the outcome of an avoided trial is unspecified and that lack of information is aversive, decreasing subjects' tendency to avoid. To examine these ideas, we here tested healthy young adults on versions of the task where avoidance responses either did or did not generate informational feedback about the optimal response. Results showed that provision of informational feedback decreased avoidance responses and also decreased categorization performance, without significantly affecting the percentage of subjects classified as "avoiders." To better understand these results, we used a modified Q-learning model to fit individual subject data. Simulation results suggest that subjects in the feedback condition adjusted their behavior faster following better-than-expected outcomes, compared to subjects in the no-feedback condition. Additionally, in both task conditions, "avoiders" adjusted their behavior faster following worse-than-expected outcomes, and treated the ambiguous no-feedback outcome as less rewarding, compared to non-avoiders. Together, results shed light on the important role of ambiguous and informative feedback in avoidance behavior.
Topics: Adult; Avoidance Learning; Behavior; Feedback; Female; Humans; Male; Punishment; Reward; Young Adult
PubMed: 26630279
DOI: 10.1371/journal.pone.0144083