Unavoidable Shock Research Articles

Between Scylla and Charybdis: Fixed-Ratio Avoidance Response Effort and Unavoidable Shock Extinction in Humans

Avoidance of potential threat may become maladaptive when it is indiscriminate and resistant to change. Here, we investigated the resistance to change of high and low avoidance response effort when avoidance extinction involved unavoidable presentations of the aversive event (shock) in humans. Following fear conditioning, participants prevented upcoming shock delivery by responding on high (i.e., fixed ratio, FR-20) and low (FR-5) negative reinforcement schedules. Next, noneliminable shock was used for an avoidance extinction procedure whereby responding was followed by, rather than prevented, shock. During a subsequent standard extinction and response prevention test phase, we found that High effort (FR-20) avoidance would be more readily extinguished than Low effort (FR-5) avoidance. It was also predicted that fear, threat expectancy, and psychophysiological (skin conductance) responses would decrease on avoidable trials and increase on unavoidable trials before extinguishing to low levels. It was found that in the final extinction re-test phase when avoidance was possible, responding increased, particularly for low effort cues. Both fear and expectancy remained high. Individual differences on clinically relevant measures of trait anxiety, intolerance of uncertainty and experiential avoidance were associated with greater levels of fear and threat expectancy. Overall, unavoidable shock extinction may hold promise for further translational investigations of avoidance learning, extinction, and clinical treatment development.

Avoidance, induction, and the illusion of reinforcement

Environmental events that impact reproductive success may be called phylogenetically important events (PIEs). Some promote reproductive success, like mates and food; others threaten reproductive success, like predators and injury. Beneficial PIEs induce activities that enhance them, and detrimental PIEs induce activities that mitigate or avoid them. Free‐operant avoidance relies on electric shock as a proxy for injury, a PIE. One theory takes avoidance behavior to be reinforced by its reducing shock rate. A more complete explanation is that avoidance both reduces shock rate and is induced by the PIEs it usually prevents. Shocks received act in concert with shock‐rate reduction, in a feedback system. Four parametric data sets were analyzed to show that avoidance is induced by received shock rate according to power functions. Avoidance is not reinforced at all; avoidance is induced by its failures. Induction explains not only avoidance itself, but also phenomena unique to avoidance, like warmup and effects of unavoidable shock. Induction explains behavior more generally than reinforcement, because induction explains not only food‐maintained operant and nonoperant behavior, but also shock‐maintained behavior, including avoidance. Reinforcement fails to explain behavior when reinforcement is defined as strengthening by consequences. Induction erases the distinction between consequences and antecedents.

Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study

SummaryBackgroundWhile the COVID-19 pandemic will increase mortality due to the virus, it is also likely to increase mortality indirectly. In this study, we estimate the additional maternal and under-5 child deaths resulting from the potential disruption of health systems and decreased access to food.MethodsWe modelled three scenarios in which the coverage of essential maternal and child health interventions is reduced by 9·8–51·9% and the prevalence of wasting is increased by 10–50%. Although our scenarios are hypothetical, we sought to reflect real-world possibilities, given emerging reports of the supply-side and demand-side effects of the pandemic. We used the Lives Saved Tool to estimate the additional maternal and under-5 child deaths under each scenario, in 118 low-income and middle-income countries. We estimated additional deaths for a single month and extrapolated for 3 months, 6 months, and 12 months.FindingsOur least severe scenario (coverage reductions of 9·8–18·5% and wasting increase of 10%) over 6 months would result in 253 500 additional child deaths and 12 200 additional maternal deaths. Our most severe scenario (coverage reductions of 39·3–51·9% and wasting increase of 50%) over 6 months would result in 1 157 000 additional child deaths and 56 700 additional maternal deaths. These additional deaths would represent an increase of 9·8–44·7% in under-5 child deaths per month, and an 8·3–38·6% increase in maternal deaths per month, across the 118 countries. Across our three scenarios, the reduced coverage of four childbirth interventions (parenteral administration of uterotonics, antibiotics, and anticonvulsants, and clean birth environments) would account for approximately 60% of additional maternal deaths. The increase in wasting prevalence would account for 18–23% of additional child deaths and reduced coverage of antibiotics for pneumonia and neonatal sepsis and of oral rehydration solution for diarrhoea would together account for around 41% of additional child deaths.InterpretationOur estimates are based on tentative assumptions and represent a wide range of outcomes. Nonetheless, they show that, if routine health care is disrupted and access to food is decreased (as a result of unavoidable shocks, health system collapse, or intentional choices made in responding to the pandemic), the increase in child and maternal deaths will be devastating. We hope these numbers add context as policy makers establish guidelines and allocate resources in the days and months to come.FundingBill & Melinda Gates Foundation, Global Affairs Canada.

Avoiding indirect effects of COVID-19 on maternal and child health

Avoiding indirect effects of COVID-19 on maternal and child health

A wake-up call: COVID-19 and its impact on children's health and wellbeing

A wake-up call: COVID-19 and its impact on children's health and wellbeing

Rat behavior and dopamine release are modulated by conspecific distress.

Rats exhibit 'empathy' making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA release in two paradigms: one that involved cues predictive of unavoidable shock to the conspecific and another that allowed the rat to refrain from reward when there were harmful consequences to the conspecific. Behavior and DA reflected pro-social interactions in that DA suppression was reduced during cues that predicted shock in the presence of the conspecific and that DA release observed on self-avoidance trials was present when the conspecific was spared. However, DA also increased when the conspecific was shocked instead of the recording rat and DA release during conspecific avoidance trials was lower than when the rat avoided shock for itself.

Involvement of the Nitrergic System of the Prefrontal Cortex in Regulating the Expression of Fear Evoked by Contextual Danger Signals

Vital intracerebral microdialysis studies in Sprague–Dawley rats showed that placing the animal in a conditioned reflex chamber in which a conditioned reflex fear response to a sound signal (combination of a tone and an unavoidable electric shock) had previously been acquired led to an increase in the extracellular citrulline (a coproduct of NO synthesis) level in the medial prefrontal cortex and induced freezing of the animal (an expression of fear). This increase was not seen in animals of the control group (same procedure, but without pain stimulation) and it was prevented by administration of the neuronal NO synthase inhibitor Nω-propyl-L-arginine (1 mM) into the medial prefrontal cortex. Administration of this substance decreased freezing induced by being placed in the conditioned reflex chamber without any effect on the rats’ mobility. These data provide evidence of the involvement of the nitrergic system of the medial prefrontal cortex in regulating the expression of fear induced by contextual danger signals.

Active place avoidance is no more stressful than unreinforced exploration of a familiar environment.

Training in the active place avoidance task changes hippocampus synaptic function, the dynamics of hippocampus local field potentials, place cell discharge, and active place avoidance memory is maintained by persistent PKMζ activity. The extent to which these changes reflect memory processes and/or stress responses is unknown. We designed a study to assess stress within the active place avoidance task by measuring serum corticosterone (CORT) at different stages of training. CORT levels did not differ between trained mice that learned to avoid the location of the mild foot shock, and untrained no-shock controls exposed to the same environment for the same amount of time. Yoked mice, that received unavoidable shocks in the same time sequence as the trained mice, had significantly higher CORT levels than mice in the trained and no-shock groups after the first trial. This increase in CORT disappeared by the fourth trial the following day, and levels of CORT for all groups matched that of home cage controls. The data demonstrate that place avoidance training is no more stressful than experiencing a familiar environment. We conclude that changes in neural function as a result of active place avoidance training are likely to reflect learning and memory processes rather than stress. © 2016 Wiley Periodicals, Inc.

Potential role of antitachycardia pacing alerts for the reduction of emergency presentations following shocks in patients with implantable cardioverter-defibrillators: implications for the implementation of remote monitoring

Despite increased use of remote monitoring (RM) to follow up implantable cardioverter-defibrillator (ICD) recipients, many patients still receive ICD shocks in the community and present to the emergency department. Our aim was to identify the best predictors of impending shock delivery that can be measured with an ICD and to identify the most appropriate activities to alert physicians to during RM follow-up. All patients presenting to our institution for ICD shock, from November 2011 to November 2014, were enrolled in this prospective study. Patient characteristics, investigation results, and details of electrical activities from ICD interrogation were recorded at presentation. Presentations were classified as potentially avoidable if activities from a list of set criteria were apparent more than 48 h before index shock. Univariate and multivariate analyses were then used to identify predictors of potentially avoidable shocks. In total, 109 emergency presentations were recorded in 90 patients (male: 85%; 57 ± 16 years; ischaemic cardiomyopathy: 49%; LVEF: 34 ± 13%; electrical storm: 40%), of which 26 (24%) were potentially avoidable. Antitachycardia pacing (ATP) episodes were the most important predictor of impending shock. Potentially avoidable shocks were preceded by more episodes of ATP than unavoidable shocks (13 [3-67] vs. 3 [0-10]; P < 0.001). Patients followed up with RM systems configured to generate alerts following ATP delivery experienced significantly less ICD shocks (24 vs. 16%, P < 0.01). Remote monitoring systems that generate alerts following ATP delivery could reduce emergency presentations for ICD shock by 24%, as ATP is a key predictor of impending shock delivery.

Aversive conditioning in honey bees (Apis mellifera anatolica): a comparison of drones and workers

Honey bees provide a model system to elucidate the relationship between sociality and complex behaviors within the same species, as females (workers) are highly social and males (drones) are more solitary. We report on aversive learning studies in drone and worker honey bees (Apis mellifera anatolica) in escape, punishment and discriminative punishment situations. In all three experiments, a newly developed electric shock avoidance assay was used. The comparisons of expected and observed responses were performed with conventional statistical methods and a systematic randomization modeling approach called object oriented modeling. The escape experiment consisted of two measurements recorded in a master-yoked paradigm: frequency of response and latency to respond following administration of shock. Master individuals could terminate an unavoidable shock triggered by a decrementing 30 s timer by crossing the shuttlebox centerline following shock activation. Across all groups, there was large individual response variation. When assessing group response frequency and latency, master subjects performed better than yoked subjects for both workers and drones. In the punishment experiment, individuals were shocked upon entering the shock portion of a bilaterally wired shuttlebox. The shock portion was spatially static and unsignalled. Only workers effectively avoided the shock. The discriminative punishment experiment repeated the punishment experiment but included a counterbalanced blue and yellow background signal and the side of shock was manipulated. Drones correctly responded less than workers when shock was paired with blue. However, when shock was paired with yellow there was no observable difference between drones and workers.

THE TIMING OF PRENATAL IMMUNE CHALLENGE DETERMINES THE EXTENT OF WHITE MATTER MICROSTRUCTURAL ANOMALIES RELEVANT TO SCHIZOPHRENIA

following transfer into the dark side they were conditioned by receiving light and tone paired with a mild unavoidable foot shock on three occasions. On return to the dark side of the chamber 24 and 48 h later the total time spent freezing was recorded to monitor learning and memory. Results: Isolated animals exhibited hyperactivity during the first 30 minutes of LMA compared with GH controls (477.7+130.6 vs 609.6+165.6 counts, respectively) but this just failed to reach statistical significance (p>0.05 by one-way ANOVA). AM630 had no significant effect on LMA. Saline injected GH rats successfully discriminated the novel object (p 0.05). GH controls froze significantly longer than SI rats irrespective of whether they had received AM630 or not both at 24 h and 48 h after the foot shock in the CER (p<0.01 by 2 way ANOVA repeated measures). Discussion: SI produced the expected hyperactivity in a novel arena and cognitive deficits in both novel object recognition and contextual fear conditioning, consistent with this being a valuable model of schizophrenia but none of these alterations were reversed by acute treatment with a CB2 receptor antagonist. CB2 receptors are possibly not involved in the long lasting behavioural defects produced by this neurodevelopmental modulation in rats.

Computational Simulation on Performance Enhancement of Cold Gas Dynamic Spray Processes With Electrostatic Assist

A real-time computational simulation on the entire cold spray process is carried out by the integrated model of compressible flow field, splat formation model, and coating formation model, in order to provide the fundamental data for the advanced high performance cold gas dynamic spray process with electrostatic acceleration. In this computation, viscous drag force, flow acceleration added mass, gravity, Basset history force, Saffman lift force, Brownian motion, thermophoresis, and electrostatic force are all considered in the particle equation of motion for the more realistic prediction of in-flight nano∕microparticle characteristics with electrostatic force and also for the detailed analysis of particle-shock-wave-substrate interaction. Computational results show that electrostatic acceleration can broaden the smallest size of applicable particle diameter for successful adhesion; as a result, wider coating can be realized. The utilization of electrostatic acceleration enhances the performance of cold dynamic spray process even under the presence of unavoidable shock wave.

Computational simulation of cold spray process assisted by electrostatic force

The integrated model of compressible thermofluid, splat formation and coating formation for the cold spray process has been established. In-flight behavior of nano-micro particles and the interaction between the shock wave and the particles in a supersonic jet flow impinging onto the substrate and further effect of electrostatic force on the particle acceleration are clarified in detail by carrying out a real-time computational simulation. The optimal particle diameters for an impinging particle velocity exceeding critical velocity exist. Particles with the diameter of submicron interact with shock wave and particles are decelerated prior to the impact. However, the particles can be accelerated considerably by utilizing electrostatic forces even in the presence of unavoidable shock waves. Finally, based on the integrated model, the coating thickness in an electrostatic assisted cold spray process is evaluated.

Efficiency of ultralow doses of antibodies to S100 protein and delta sleep-inducing peptide in rats with anxious depression.

We studied the effects of single peroral treatment with antibodies against S100 protein and delta sleep-inducing peptide in ultralow doses on behavioral characteristics of rats with anxious depression produced by acute stress (unavoidable electrical shock). Stress-produced behavioral changes and anxiolytic activity of antibodies were determined using the elevated plus-maze, open field, and tail suspension tests. High efficiency of the mixture of antibodies against S100 protein and delta sleep-inducing peptide was observed in all tests. Anxiolytic activity of anti-S100 antibodies (although less pronounced than that of the mixture of antibodies) was revealed in the elevated plus-maze and tail suspension test.

Fatal &lt;i&gt;Yersinia enterocolitica&lt;/i&gt; Septicemia after Transfusion of Red Cells – Case Report and Review of the Literature

Whereas up to 10% (median: 0.046-0.1%) of platelet concentrates are regarded to be bacterially contaminated, approximately only one out of 9 million transfused red blood cell (RBC) units bears the chance of death from sepsis due to contamination with psychrophilic bacteria, mainly &lt;i&gt;Yersiniα enterocoliticα. &lt;/i&gt;We report the clinical course and the bacteriological examination of unavoidable fatal septic shock resulting from transfusion of a RBC unit contaminated with &lt;i&gt;Y. enterocoliticα &lt;/i&gt;in a 47-year-old man who underwent cystectomy due to bladder cancer. The case is discussed in the light of different recommended measures during collecting and processing of blood donations that could be suitable to prevent bacterial contamination.

Desensitization of the D 1 dopamine receptors in rats reproduces a model of escape deficit reverted by imipramine, fluoxetine and clomipramine

1. 1. The present study investigated the effect of long-term D 1 dopamine receptor stimulation on an animal model of depression derived from the learned helplessness paradigm. 2. 2. The model used is based on the escape deficit produced by a series of unavoidable shocks administered to rats 24 h before the test session. SKF 38393 administered acutely, completely prevented the development of animal hyporeactivity, while given repeatedly produced tolerance to its own protective effect. Moreover it also reduced the spontaneous escape reactivity of rats not exposed to the inescapable shocks. Animals chronically receiving SKF 38393 and showing a clearcut escape deficit, were treated daily with either imipramine, fluoxetine, or clomipramine. After 21 days of combined treatment the 3 antidepressants appeared equally effective in reverting the behavioral deficit. Moreover, long term administration of both imipramine or SKF 38393 down regulated D 1 dopamine receptor number in the prefrontal cortex, while the association of the two drugs resulted in a receptor density similar to that of control rats. 3. 3. The present results further support the crucial role played by di dopamine receptors in the control of animal reactivity to stressful stimuli and in the mechanism of action of imipramine. Moreover they show that the D 1 dopamine receptor related escape deficit is sensitive also to compounds selectively acting through the serotonergic neuronal system.

Repeated unavoidable shocks induce and maintain a condition of escape deficit which is reversed by antidepressants

Repeated unavoidable shocks induce and maintain a condition of escape deficit which is reversed by antidepressants

Crucial role of D 1 dopamine receptors in mediating the antidepressant effect of imipramine

Although the neurochemical effects of chronic imipramine (IMI) treatment have been related to an increased adrenergic as well as dopaminergic transmission, no clear-cut evidence exists on whether one of these two neuronal systems mediates the behavioral effects of the tricyclic compound. Because a large body of evidence favors the role of dopamine, the interference of a selective inhibition of D 1 or D 2 D 3 dopamine receptors on IMI effect upon the learned helplessness behavior (LH) in rats was studied. A 2-week treatment with SCH 23390, followed by a 24-h washout, showed almost the same efficacy as chronic IMI in preventing LH induction. Moreover, SCH 23390 given acutely before the pretest completely antagonized the effect of chronic IMI. Furthermore, SKF 38393 administered to drug-naive animals prior to the unavoidable shocks completely neutralized its behavioral sequelae. Finally, the inhibition of D 2 D 3 dopamine receptors by acute sulpiride did not modify IMI efficacy. These results strongly suggest that D 1 dopamine receptor function controls the reactivity of animals exposed to a prolonged unavoidable stress, and mediates IMI antidepressant effect.

Imipramine and fluoxetine prevent the stress-induced escape deficits in rats through a distinct mechanism of action

A large body of evidence indicates that brain monoamines are involved in the pathogenesis of mental depression, as well as in the mechanism of action of most antidepressant treatments. The present report shows that long-term exposure to imipramine (IMI) or fluoxetine (FLX) was equally potent in preventing the escape deficits produced in rats by repeated unavoidable shocks. The acute administration of SCH 23390, a selective D1 dopamine receptor blocker, shortly before the inescapable shock session, entirely prevented IMI effect on escape performance, but only partially prevented that of FLX. Moreover, pindolol (an antagonist of beta-adrenoceptors and of serotonin 5-HT(1A) and 5-HT(1B) receptors) completely antagonized the efficacy of FLX in preventing escape deficits, whereas it did not effect the activity of IMI. The acute administration of propranolol failed to alter the effect of either antidepressant. It was concluded that in rats, the efficacy of IMI in counteracting the stress-induced behavioral sequelae is mainly mediated by the activation of D1 dopamine receptors, whereas that of FLX is largely dependent upon the stimulation of post-synaptic 5-HT(1A) receptors. Finally, the effects of the two drugs appear to be totally unrelated to activation of beta-adrenoceptors.

Divergent responses to long-term stressors in rat lines selected for different functional states of the nervous system

The conditioned and reflex parameters in rat lines selected for the threshold of excitability (a fundamental characteristics of the functional state of the nervous system) were estimated. This measure is based on the response of the tibial nerve to electrical stimulation, which gives a general indication of the level of excitability of other parts of the nervous system. Testing was made 1-3 days after 15 days of daily stress caused by randomly presented pairing of light and unavoidable electric shock. Expression of the sensitivity to the electric current, and the reflex components of the behavior, depends on the genetically determined level of the functional state of the nervous system.