Stimulus Exposure Research Articles

Transcutaneous Auricular Vagus Nerve Stimulation for Visually Induced Motion Sickness: An eLORETA Study

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive form of electrical brain stimulation, has shown potent therapeutic potential for a wide spectrum of conditions. How taVNS influences the characterization of motion sickness – a long mysterious syndrome with a polysymptomatic onset – remains unclear. Here, to examine taVNS-induced effects on brain function in response to motion-induced nausea, 64-channel electroencephalography (EEG) recordings from 42 healthy participants were analyzed; collected during nauseogenic visual stimulation concurrent with taVNS administration, in a crossover randomized sham-controlled study. Cortical neuronal generators were estimated from the obtained EEG using exact low-resolution brain electromagnetic tomography (eLORETA). While both sham and taVNS increased insula activation during electrical stimulation, compared to baseline, taVNS additionally augmented middle frontal gyrus neuronal activity. Following taVNS, brain regions including the supramarginal, parahippocampal, and precentral gyri were activated. Contrasting sham, taVNS markedly increased activity in the middle occipital gyrus during stimulation. A repeated-measures ANOVA showed that taVNS reduced motion sickness symptoms. This reduction in symptoms correlated with taVNS-induced neural activation. Our findings provide new insights into taVNS-induced brain changes, during and after nauseogenic stimuli exposure, including accompanying behavioral response. Together, these findings suggest that taVNS has promise as an effective neurostimulation tool for motion sickness management.

Investigating the human capabilities for intuitive evaluation of component manufacturability

This article explores the intersection of Design for Manufacturing (DFM) principles and human cognition in component manufacturability. In the context of contemporary manufacturing challenges, where design and manufacturing departments often operate separately, this study aims to bridge the gap by investigating human capabilities in intuitively assessing manufacturability during the design phase. Research employs experimental trials with visual stimuli representing various part designs, categorizing them based on adherence to DFM rules. Participants, without prior formal education in DFM, are tasked with choosing the more manufacturable component within a pair. Results indicate that a majority of participants demonstrate an innate ability to make correct manufacturability assessments. Additionally, the study evaluates the impact of stimulus exposure time on participant performance. These findings provide valuable insights into the intuitive aspects of human manufacturability assessment and lay the groundwork for further research, including larger participant groups and deeper exploration of decision-making processes and knowledge types involved in DFM practices. The main contribution of presented study involves showcasing human capabilities for component manufacturability assessment with the use of intuitive thinking and quick decision-making in place of following strict rulesets and design principles.

Stimulus repetition induces a two-stage learning process in primary visual cortex.

Repeated stimulus exposure alters the brain's response to the stimulus. We investigated the underlying neural mechanisms by recording functional MRI data from human observers passively viewing 120 presentations of two Gabor patches (each Gabor repeating 60 times). We evaluated support for two prominent models of stimulus repetition, the fatigue model and the sharpening model. Our results uncovered a two-stage learning process in the primary visual cortex. In Stage 1, univariate BOLD activation in V1 decreased over the first twelve repetitions of the stimuli, replicating the well-known effect of repetition suppression. Applying MVPA decoding along with a moving window approach, we found that (1) the decoding accuracy between the two Gabors decreased from above-chance level (∼60% to ∼70%) at the beginning of the stage to chance level at the end of the stage (∼50%). This result, together with the accompanying weight map analysis, suggested that the learning dynamics in Stage 1 were consistent with the predictions of the fatigue model. In Stage 2, univariate BOLD activation for the remaining 48 repetitions of the two stimuli exhibited significant fluctuations but no systematic trend. The MVPA decoding accuracy between the two Gabor patches was at chance level initially and became progressively higher as stimulus repetition continued, rising above and staying above chance level starting at the ∼35th repetition. Thus, results from the second stage supported the notion that sustained and prolonged stimulus repetition prompts sharpened representations. Additional analyses addressed (1) whether the neural patterns within each learning stage remained stable and (2) whether new neural patterns were evoked in Stage 2 relative to Stage 1.

Differentiation responses to matched stress stimulus exposures show that the differentiation to 1st lineage of TSC is vastly greater than that of ESC.

Differentiation responses to matched stress stimulus exposures show that the differentiation to 1st lineage of TSC is vastly greater than that of ESC.

Identification of a stress-responsive subregion of the basolateral amygdala in male rats.

The basolateral amygdala (BLA) is reliably activated by psychological stress and hyperactive in conditions of pathological stress or trauma; however, subsets of BLA neurons are also readily activated by rewarding stimuli and can suppress fear and avoidance behaviours. The BLA is highly heterogeneous anatomically, exhibiting continuous molecular and connectivity gradients throughout the entire structure. A critical gap remains in understanding the anatomical specificity of amygdala subregions, circuits, and cell types explicitly activated by acute stress and how they are dynamically activated throughout stimulus exposure. Using a combination of topographical mapping for the activity-responsive protein FOS and fiber photometry to measure calcium transients in real-time, we sought to characterize the spatial and temporal patterns of BLA activation in response to a range of novel stressors (shock, swim, restraint, predator odour) and non-aversive, but novel stimuli (crackers, citral odour). We report four main findings: (1) the BLA exhibits clear spatial activation gradients in response to novel stimuli throughout the medial-lateral and dorsal-ventral axes, with aversive stimuli strongly biasing activation towards medial aspects of the BLA; (2) novel stimuli elicit distinct temporal activation patterns, with stressful stimuli exhibiting particularly enhanced or prolonged temporal activation patterns; (3) changes in BLA activity are associated with changes in behavioural state; and (4) norepinephrine enhances stress-induced activation of BLA neurons via the ß-noradrenergic receptor. Moving forward, it will be imperative to combine our understanding of activation gradients with molecular and circuit-specificity.

Distinct Neural Plasticity Enhancing Visual Perception.

The developed human brain shows remarkable plasticity following perceptual learning, resulting in improved visual sensitivity. However, such improvements commonly require extensive stimuli exposure. Here we show that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural mechanisms relative to standard repetition-based learning. Participants (n = 20, 12 women, 8 men) encoded a visual discrimination task, followed by brief memory reactivations of only five trials each performed on separate days, demonstrating improvements comparable with standard repetition-based learning (n = 20, 12 women, 8 men). Reactivation-induced learning engaged increased bilateral intraparietal sulcus (IPS) activity relative to repetition-based learning. Complementary evidence for differential learning processes was further provided by temporal-parietal resting functional connectivity changes, which correlated with behavioral improvements. The results suggest that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural processes, engaging higher-order control and attentional resources while leading to similar perceptual gains. These unique brain mechanisms underlying improved perceptual learning efficiency may have important implications for daily life and in clinical conditions requiring relearning following brain damage.

Delayed Pressure Urticaria Associated With Altitude Chamber Training Responsive to Cyclosporine and Omalizumab.

Delayed pressure urticaria (DPU) is a subset of chronic inducible urticaria. It is characterized by the formation of wheals anytime between 30 minutes and 24 hours after stimulus exposure of localized pressure application. In this case report, we discuss a military flight crew member with no significant past medical history who developed DPU following rapid decompression in an altitude chamber. The chamber training included an uneventful ascent to 45,000 feet, higher than he had been previously, and a rapid decompression. About 16 hours later, he developed pruritic swelling of his hands and feet, along with diffuse deep nodular swelling, erythematous plaques, and erythematous nodules. His DPU was refractory to monotherapy treatment with antihistamines, and he continued to develop lesions in weight-bearing areas. Control of symptoms was achieved through combination treatment of a second-generation antihistamine, a leukotriene receptor antagonist, and an immunosuppressant (cyclosporine). His waiver to return to flight status was denied while on cyclosporine. He was transitioned to a monoclonal antibody that binds free immunoglobin E (omalizumab) with resolution of symptoms and was cleared to return to active duty.

Effects of acute inhibition of dopamine β-hydroxylase on neural responses to pups in adult virgin male California mice (Peromyscus californicus)

The neural mechanisms underlying paternal care in biparental mammals are not well understood. The California mouse (Peromyscus californicus) is a biparental rodent in which virtually all fathers are attracted to pups, while virgin males vary widely in their behavior toward unrelated infants, ranging from attacking to avoiding to huddling and grooming pups. We previously showed that pharmacologically inhibiting the synthesis of the neurotransmitter norepinephrine (NE) with the dopamine β-hydroxylase inhibitor nepicastat reduced the propensity of virgin male and female California mice to interact with pups. The current study tested the hypothesis that nepicastat would reduce pup-induced c-Fos immunoreactivity, a cellular marker of neural activity, in the medial preoptic area (MPOA), medial amygdala (MeA), basolateral amygdala (BLA), and bed nucleus of the stria terminalis (BNST), brain regions implicated in the control of parental behavior and/or anxiety. Virgin males were injected with nepicastat (75 mg/kg, i.p.) or vehicle 2 hours prior to exposure to either an unrelated pup or novel object for 60 minutes (n = 4–6 mice per group). Immediately following the 60-minute stimulus exposure, mice were euthanized and their brains were collected for c-Fos immunohistochemistry. Nepicastat reduced c-Fos expression in the MeA and MPOA of pup-exposed virgin males compared to vehicle-injected controls. In contrast, nepicastat did not alter c-Fos expression in any of the above brain regions following exposure to a novel object. Overall, these results suggest that the noradrenergic system might influence MeA and MPOA function to promote behavioral interactions with pups in virgin males.

Burst firing in Output-Defined Parallel Habenula Circuit Underlies the Antidepressant Effects of Bright Light Treatment.

Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN-projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.

Early‐life and chronic exposure to high‐fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges

AbstractChildhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high‐fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

C57BL/6J offspring mice reared by a single-mother exhibit, compared to mice reared in a biparental parenting structure, distinct neural activation patterns and heightened ethanol-induced anxiolysis.

Parenting experiences with caregivers play a key role in neurodevelopment. We recently reported that adolescents reared by a single-mother (SM) display an anxiety-prone phenotype and drink more alcohol, compared to peers derived from a biparental (BP) rearing condition. To investigate if SM and BP offspring infant mice exhibit differential sensitivity to ethanol-induced locomotor activity and differential activity patterns in brain areas related to anxiety response. We also analyzed anxiety response and ethanol-induced anxiolysis in SM and BP adolescents. Mice reared in SM or BP conditions were assessed for (a) ethanol-induced locomotor activity at infancy, (b) central expression of Fos-like proteins (likely represented mostly by FosB, a transcription factor that accumulates after chronic stimuli exposure and serves as a molecular marker of neural plasticity) and cathecolaminergic activity, and (c) anxiety-like behavior and ethanol-induced anxiolysis in adolescence. Infant mice were sensitive to the stimulating effects of 2.0g/kg alcohol, regardless parenting structure. SM mice exhibited, relative to BP mice, a significantly greater number of Fos-like positive cells in the central amygdala and basolateral amygdala nuclei. Ethanol treatment, but not parenting condition, induced greater activation of dopaminergic neurons in ventral tegmental area. SM, but not BP, adolescent mice were sensitive to ethanol-induced anxiolysis. These results highlight the complex relationship between parenting experiences and neurodevelopment. The SM parenting may result in greater neural activation patterns in brain areas associated with anxiety response, potentially contributing to increased basal anxiety and alcohol sensitivity.

The reliability of Hebb repetition learning and its association with language and reading in adolescents with intellectual disabilities

Hebb repetition learning (HRL) refers to neurodevelopmental processes characterised by repeated stimulus exposure without feedback, which result in changes in behaviour and/or responses, e.g., long-term learning of serial order. Here, we investigate effects of HRL on serial order memory. The present research aimed to assess the reliability of new HRL measures and investigate their relationships with language and reading skills (vocabulary, grammar, word reading) in adolescents with intellectual disability (ID). A comparison group of children of similar mental age with typical development (TD) was also assessed. ID and TD groups were tested on HRL tasks, evaluating test-retest and split-half reliability. The relationship between HRL and language and reading was analysed after accounting for the influence of mental age and verbal short-term memory. The HRL tasks displayed moderate test-retest (and split-half) reliability, HRL tasks with different stimuli (verbal, visual) were related, and we identified issues with one method of HRL scoring. The planned regression analyses failed to show relationships between HRL and language/reading skills in both groups when mental age, a very strong predictor, was included. However, further exploratory regression analyses without mental age revealed HRL's predictive capabilities for vocabulary in the ID group and reading in the TD group, results which need further investigation and replication. HRL displays promise as a moderately reliable metric and exhibits varied and interpretable predictive capabilities for language and reading skills across groups.

Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation

BackgroundChronic pruritus (CP) is a poorly characterized condition associated with intense pruritus without a primary skin eruption. This condition tends to emerge more commonly in older adults, and there is limited research on triggering factors. ObjectiveTo explore the clinical characteristics and pathophysiology of chronic pruritus following exposure to an immune stimulus. MethodsClinical characteristics and plasma samples were collected from 15 patients who developed CP following an immune stimulus such as checkpoint inhibitors or vaccination. A multiplex panel was used to analyze plasma cytokine concentrations within these patients. ResultsMost immunotherapy-treated patients experienced CP during treatment or after 21 to 60 days of receiving treatment, while vaccine-stimulated patients developed pruritus within a week of vaccination. Plasma cytokine analysis revealed elevated levels of twelve cytokines in patients with immune-stimulated CP compared to healthy controls. Notably, Th2-related cytokines IL-5 (FC 2.65; q<0.25) and TSLP (FC 1.61 q<0.25) were upregulated. LimitationsLimitations of this study include limited sample size, particularly in the plasma cytokine assay. Conclusions and RelevanceThis study reveals triggers of CP development and describes alterations in blood Th2 markers in CP patients, including IgE, increased blood eosinophils, and cytokines IL-5 and TSLP.

Interfering with reconsolidation by rimonabant results in blockade of heroin-associated memory.

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder.

The processing of spatial frequencies through time in visual word recognition

This study examined the temporal profile of spatial frequency processing in a word reading task in 16 normal adult readers. They had to report the word presented in a 200 ms display using a four-alternative forced-choice task (4AFC). The stimuli were made of an additive combination of the signal (i.e. the target word) and of a visual white noise patch wherein the signal-to-noise ratio varied randomly across stimulus duration. Four spatial frequency conditions were defined for the signal component of the stimulus (bandpass Butterworth filters with center frequencies of 1.2, 2.4, 4.8 and 9.6 cycles per degree). In contrast to the coarse-to-fine theory of visual recognition, the results show that the highest spatial frequency range dominates early processing, with a shift toward lower spatial frequencies at later points during stimulus exposure. This pattern interacted in a complex way with the temporal frequency content of signal-to-noise oscillations. The outcome of individual data patterns classification by a machine learning algorithm according to the corresponding spatial frequency band further shows that the most salient spatial frequency signature is obtained when the time dimension within data patterns is recoded into its Fourier transform.

A stimulus exposure of 50 ms elicits the uncanny valley effect

The uncanny valley (UV) effect captures the observation that artificial entities with near-human appearances tend to create feelings of eeriness. Researchers have proposed many hypotheses to explain the UV effect, but the visual processing mechanisms of the UV have yet to be fully understood. In the present study, we examined if the UV effect is as accessible in brief stimulus exposures compared to long stimulus exposures (Experiment 1). Forty-one participants, aged 21–31, rated each human-robot face presented for either a brief (50 ms) or long duration (3 s) in terms of attractiveness, eeriness, and humanness (UV indices) in a 7-point Likert scale. We found that brief and long exposures to stimuli generated a similar UV effect. This suggests that the UV effect is accessible at early visual processing. We then examined the effect of exposure duration on the categorisation of visual stimuli in Experiment 2. Thirty-three participants, aged 21–31, categorised faces as either human or robot in a two-alternative forced choice task. Their response accuracy and variance were recorded. We found that brief stimulus exposures generated significantly higher response variation and errors than the long exposure condition. This indicated that participants were more uncertain in categorising faces in the brief exposure condition due to insufficient time. Further comparisons between Experiment 1 and 2 revealed that the eeriest faces were not the hardest to categorise. Overall, these findings indicate (1) that both the UV effect and categorical uncertainty can be elicited through brief stimulus exposure, but (2) that categorical uncertainty is unlikely to cause the UV effect. These findings provide insights towards the perception of robotic faces and implications for the design of robots, androids, avatars, and artificial intelligence agents.

A rapid procedure to assess shifts in discriminative control over drinking during recovery-like behavior

BackgroundPreviously, we reported that recovery-like behavior decreases stimulus control over drinking, and this likely plays a role in the clinical observation that longer recovery increases relapse resistance. Those studies were conducted using a procedure that required repeated assessment, preventing a longitudinal analysis of the changes in stimulus control over time in each individual. Here we recapitulate those results and extend them to female rats using a more efficient procedure that allows repeated assessment of changes in stimulus control over drinking during recovery. MethodsUnder a multiple concurrent schedule, rats were trained to reliably respond predominantly for ethanol (concurrent Ethanol FR5, Food FR150) in the presence of one stimulus and for food (concurrent Ethanol FR5, Food FR5) in the presence of another stimulus. Stimuli were either lights or tones, depending on the group. After that, a drinking phase in which only the stimulus occasioning ethanol responding was presented (10 or 20 sessions) followed by recovery-like sessions in which only the stimulus occasioning food responding was presented. During these sessions, rats were exposed to the ethanol stimulus under extinction during the first component on sessions 0, 1, 2, 4, 8, and 16. The number of food responses during these stimulus exposures prior to the first five ethanol responses was the primary measure. ResultsConsistent with the earlier procedure, the number of food responses during ethanol tests increased as a function of the number of recovery sessions completed, regardless of whether the stimuli were visual or auditory. However, there were no significant effects of extended alcohol exposure or sex. ConclusionsA rapid procedure consistent with the earlier procedure and clinical evidence was developed in which stimulus control over drinking decreased following longer periods of recovery. Under conditions tested, stimulus type, length of drinking history, and sex did not affect this relationship.

Latent inhibition in humans from simple stimulus exposure.

Two experiments observed an effect consistent with a latent-inhibition (LI) effect in humans that (a) did not depend on masking or instruction-generated expectations and (b) suggested that the effect results from a change in processing of the predictive cue. Participants viewed a video of a superhero character flying through three different contexts past a different stimulus in each context. In conditioning, The superhero flew past a target cue that was either Novel (Group No Exposure), had been preexposed in the Same context as where conditioning was occurring (Group Same), or was preexposed in a Different context (Group Different). Each time the superhero flew past the target cue his Hands Glowed (outcome). On test (E1), an image of the superhero flying in the context with normal Hands and the target cue was present. Participants were asked if anything was missing. Experiment 2 tested participants with the superhero present and his Hands Glowing to test outcome-cue associations (Test 1) or just the superhero in the context (Test 2, counterbalanced) to assess contextual associations. In E1 fewer people in Group Same reported the outcome missing than Group No Exposure or Group Different. In E2 fewer people in Group Same reported the target cue missing when presented with the outcome than in the other groups, a result inconsistent with interference accounts of LI. When presented only with contextual cues, reports of the stimulus missing showed that the context was associated with the stimuli presented within it. Results are discussed with respect to theories and demonstrations of human LI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding the role of emotion in decision making process: using machine learning to analyze physiological responses to visual, auditory, and combined stimulation.

Emotions significantly shape decision-making, and targeted emotional elicitations represent an important factor in neuromarketing, where they impact advertising effectiveness by capturing potential customers' attention intricately associated with emotional triggers. Analyzing biometric parameters after stimulus exposure may help in understanding emotional states. This study investigates autonomic and central nervous system responses to emotional stimuli, including images, auditory cues, and their combination while recording physiological signals, namely the electrocardiogram, blood volume pulse, galvanic skin response, pupillometry, respiration, and the electroencephalogram. The primary goal of the proposed analysis is to compare emotional stimulation methods and to identify the most effective approach for distinct physiological patterns. A novel feature selection technique is applied to further optimize the separation of four emotional states. Basic machine learning approaches are used in order to discern emotions as elicited by different kinds of stimulation. Electroencephalographic signals, Galvanic skin response and cardio-respiratory coupling-derived features provided the most significant features in distinguishing the four emotional states. Further findings highlight how auditory stimuli play a crucial role in creating distinct physiological patterns that enhance classification within a four-class problem. When combining all three types of stimulation, a validation accuracy of 49% was achieved. The sound-only and the image-only phases resulted in 52% and 44% accuracy respectively, whereas the combined stimulation of images and sounds led to 51% accuracy. Isolated visual stimuli yield less distinct patterns, necessitating more signals for relatively inferior performance compared to other types of stimuli. This surprising significance arises from limited auditory exploration in emotional recognition literature, particularly contrasted with the pleathora of studies performed using visual stimulation. In marketing, auditory components might hold a more relevant potential to significantly influence consumer choices.

Shifts in stimulus control over opioid use with increasing periods of recovery

BackgroundPeriods of engaging in an alternative behavior diminishes behavioral control by stimuli occasioning alcohol use. This increase in relapse resistance with increasing recovery suggests that changing stimulus control over substance use may be a mechanism responsible for decreased relapse rates with longer recovery. However, the generality of this phenomenon to other drugs of abuse, including opioid self-administration, remains unclear. This study tests the generality of these findings with etonitazene to determine whether the shift in attention represents a behavioral process that generalizes from conditions we previously reported. MethodsFive adult male Lewis rats were trained to respond on levers under two stimulus conditions; high-cost food (food FR150 and etonitazene FR5) and low-cost food (both food and etonitazene FR 5). Next, only the high-cost food stimulus (occasioning etonitazene responding) was presented for 20 sessions (Use Phase) followed by 9 sessions in which only the low-cost food stimulus (occasioning food responding) was presented (Recovery Phase). During the Recovery Phase, testing occurred during the first component of sessions 0, 1, 2, 4, and 8 when rats were re-exposed to the high-cost food stimulus. The number of food responses prior to completing the etonitazene response requirement during this stimulus exposure was the primary measure. ResultsFood responses during stimulus re-exposure increased significantly as a function of recovery sessions completed with a slope [95 % CI] of 2.49 responses/recovery session [0.16, 4.81]. The average number of etonitazene deliveries per use session was 32 ± 6.6 or an average daily dose of 48.8 ± 10.1 μg/kg. During Recovery Phase, etonitazene deliveries decreased to 2.4 ± 1 or 3.6 ± 1.5 μg/kg. ConclusionThe decrease in stimulus control observed for ethanol self-administration appears to generalize to opioid self-administration, indicating this change in stimulus control may play a general role in recovery.