Browsing by Subject "Avoidance Learning"
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Item Open Access An operant-based detection method for inferring tinnitus in mice.(Journal of neuroscience methods, 2017-11) Zuo, Hongyan; Lei, Debin; Sivaramakrishnan, Shobhana; Howie, Benjamin; Mulvany, Jessica; Bao, JianxinBackground
Subjective tinnitus is a hearing disorder in which a person perceives sound when no external sound is present. It can be acute or chronic. Because our current understanding of its pathology is incomplete, no effective cures have yet been established. Mouse models are useful for studying the pathophysiology of tinnitus as well as for developing therapeutic treatments.New method
We have developed a new method for determining acute and chronic tinnitus in mice, called sound-based avoidance detection (SBAD). The SBAD method utilizes one paradigm to detect tinnitus and another paradigm to monitor possible confounding factors, such as motor impairment, loss of motivation, and deficits in learning and memory.Results
The SBAD method has succeeded in monitoring both acute and chronic tinnitus in mice. Its detection ability is further validated by functional studies demonstrating an abnormal increase in neuronal activity in the inferior colliculus of mice that had previously been identified as having tinnitus by the SBAD method.Comparison with existing methods
The SBAD method provides a new means by which investigators can detect tinnitus in a single mouse accurately and with more control over potential confounding factors than existing methods.Conclusion
This work establishes a new behavioral method for detecting tinnitus in mice. The detection outcome is consistent with functional validation. One key advantage of mouse models is they provide researchers the opportunity to utilize an extensive array of genetic tools. This new method could lead to a deeper understanding of the molecular pathways underlying tinnitus pathology.Item Open Access Effects of sub-chronic methylphenidate on risk-taking and sociability in zebrafish (Danio rerio).(Naunyn-Schmiedeberg's archives of pharmacology, 2020-08) Brenner, Rebecca G; Oliveri, Anthony N; Sinnott-Armstrong, Walter; Levin, Edward DAttention deficit hyperactive disorder (ADHD) is the most common psychiatric disorder in children affecting around 11% of children 4-17 years of age (CDC 2019). Children with ADHD are widely treated with stimulant medications such as methylphenidate (Ritalin®). However, there has been little research on the developmental effects of methylphenidate on risk-taking and sociability. We investigated in zebrafish the potential developmental neurobehavioral toxicity of methylphenidate on these behavioral functions. We chose zebrafish because they provide a model with extensive genetic tools for future mechanistic studies. We studied whether sub-chronic methylphenidate exposure during juvenile development causes neurobehavioral impairments in zebrafish. Methylphenidate diminished responses to environmental stimuli after both acute and sub-chronic dosing. In adult zebrafish, acute methylphenidate impaired avoidance of an approaching visual stimulus modeling a predator and decreased locomotor response to the social visual stimulus of conspecifics. Adult zebrafish dosed acutely with methylphenidate demonstrated behaviors of less retreat from threatening visual stimuli and less approach to conspecifics compared with controls. In a sub-chronic dosing paradigm during development, methylphenidate caused less robust exploration of a novel tank. In the predator avoidance paradigm, sub-chronic dosing that began at an older age (28 dpf) decreased activity levels more than sub-chronic dosing that began at earlier ages (14 dpf and 21 dpf). In the social shoaling task, sub-chronic methylphenidate attenuated reaction to the social stimulus. Acute and developmental methylphenidate exposure decreased response to environmental cues. Additional research is needed to determine critical mechanisms for these effects and to see how these results may be translatable to neurobehavioral toxicity of prescribing Ritalin® to children and adolescents.Item Open Access Fear, avoidance and physiological symptoms during cognitive-behavioral therapy for social anxiety disorder.(Behav Res Ther, 2013-07) Aderka, Idan M; McLean, Carmen P; Huppert, Jonathan D; Davidson, Jonathan RT; Foa, Edna BWe examined fear, avoidance and physiological symptoms during cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD). Participants were 177 individuals with generalized SAD who underwent a 14-week group CBT as part of a randomized controlled treatment trial. Participants filled out self-report measures of SAD symptoms at pre-treatment, week 4 of treatment, week 8 of treatment, and week 14 of treatment (post-treatment). Cross-lagged Structural Equation Modeling indicated that during the first 8 weeks of treatment avoidance predicted subsequent fear above and beyond previous fear, but fear did not predict subsequent avoidance beyond previous avoidance. However, during the last 6 weeks of treatment both fear and avoidance predicted changes in each other. In addition, changes in physiological symptoms occurred independently of changes in fear and avoidance. Our findings suggest that changes in avoidance spark the cycle of change in treatment of SAD, but the cycle may continue to maintain itself through reciprocal relationships between avoidance and fear. In addition, physiological symptoms may change through distinct processes that are independent from those involved in changes of fear and avoidance.Item Open Access Investigating dynamic pain sensitivity in the context of the fear-avoidance model.(Eur J Pain, 2015-01) Gay, CW; Horn, ME; Bishop, MD; Robinson, ME; Bialosky, JEBACKGROUND: Although nearly everyone at some point in their lives experiences back pain; the amount of interference with routine activity varies significantly. The fear-avoidance (FA) model of chronic pain explains how psychological variables, such as fear, act as mediating factors influencing the relationship between clinical pain intensity and the amount of interference with daily activities. What remains less clear is how other mediating factors fit within this model. The primary objective of this report was to examine the extent to which a dynamic measure of pain sensitivity provides additional information within the context of the FA model. METHOD: To address our primary objective, classic mediation and moderated mediation analyses were conducted on baseline clinical, psychological and quantitative sensory measures obtained on 67 subjects with back pain (mean age, 31.4 ± 12.1 years; 70% female). RESULTS: There was a moderately strong relationship (r = 0.52; p < 0.01) between clinical pain intensity and interference, explaining about 27% of the variance in the outcome. Mediation analyses confirmed fear partially mediated the total effect of clinical pain intensity on interference (Δβ = 0.27; p < 0.01), and accounted for an additional 16% of the variance. In our FA model, pain sensitivity did not demonstrate additional indirect effects; however, it did moderate the strength of indirect effects of fear. CONCLUSION: This preliminary modelling suggests complex interactions exist between pain-related fear and pain sensitivity measures that further explain individual differences in behaviour.Item Open Access The impact of structured support groups for pregnant South African women recently diagnosed HIV positive.(Women Health, 2011-08-31) Mundell, Jonathan P; Visser, Maretha J; Makin, Jennifer D; Kershaw, Trace S; Forsyth, Brian WC; Jeffery, Bridget; Sikkema, Kathleen JThe authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women. Participants were expected to display increases in HIV disclosure, self-esteem, active coping and positive social support, and decreases in depression, avoidant coping, and negative social support. Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006. Using a quasi-experimental design, assessments were conducted at baseline and two and eight months post-intervention. A series of random effects regression analyses were conducted, with the three assessment points treated as a random effect of time. At both follow-ups, the rate of disclosure in the intervention group was significantly higher than that of the comparison group (p<0.001). Compared to the comparison group at the first follow-up, the intervention group displayed higher levels of active coping (t=2.68, p<0.05) and lower levels of avoidant coping (t=-2.02, p<0.05), and those who attended at least half of the intervention sessions exhibited improved self-esteem (t=2.11, p<0.05). Group interventions tailored for newly HIV positive pregnant women, implemented in resource-limited settings, may accelerate the process of adjusting to one's HIV status, but may not have sustainable benefits over time.Item Open Access TRPV channel-mediated calcium transients in nociceptor neurons are dispensable for avoidance behaviour.(Nat Commun, 2014-09-02) Lindy, Amanda S; Parekh, Puja K; Zhu, Richard; Kanju, Patrick; Chintapalli, Sree V; Tsvilovskyy, Volodymyr; Patterson, Randen L; Anishkin, Andriy; van Rossum, Damian B; Liedtke, Wolfgang BAnimals need to sense and react to potentially dangerous environments. TRP ion channels participate in nociception, presumably via Ca(2+) influx, in most animal species. However, the relationship between ion permeation and animals' nocifensive behaviour is unknown. Here we use an invertebrate animal model with relevance for mammalian pain. We analyse the putative selectivity filter of OSM-9, a TRPV channel, in osmotic avoidance behaviour of Caenorhabditis elegans. Using mutagenized OSM-9 expressed in the head nociceptor neuron, ASH, we study nocifensive behaviour and Ca(2+) influx. Within the selectivity filter, M(601)-F(609), Y604G strongly reduces avoidance behaviour and eliminates Ca(2+) transients. Y604F also abolishes Ca(2+) transients in ASH, while sustaining avoidance behaviour, yet it disrupts behavioral plasticity. Homology modelling of the OSM-9 pore suggests that Y(604) may assume a scaffolding role. Thus, aromatic residues in the OSM-9 selectivity filter are critical for pain behaviour and ion permeation. These findings have relevance for understanding evolutionary roots of mammalian nociception.