The role of loss aversion in social conformity: psychological and neural representations.

The impact of others' choices on decision-making is influenced by individual preferences. However, the specific roles of individual preferences in social decision-making remain unclear. In this study, we examine the contributions of risk and loss preferences as well as social influence in decision-making under uncertainty using a gambling task. Our findings indicate that while both individual preferences and social influence affect decision-making in social contexts, loss aversion plays a dominant role, especially in individuals with high loss aversion. This phenomenon is accompanied by increased functional connectivity between the anterior insular cortex and the temporoparietal junction. These results highlight the critical involvement of loss aversion and the anterior insular cortex-temporoparietal junction neural pathway in social decision-making under uncertainty. Our findings provide a computational account of how individual preferences and social information collectively shape our social decision-making behaviors.

Sturnidae sensu lato Mitogenomics: Novel Insights into Codon Aversion, Selection, and Phylogeny.

The Sturnidae family comprises 123 recognized species in 35 genera. The taxa Mimidae and Buphagidae were formerly treated as subfamilies within Sturnidae. The phylogenetic relationships among the Sturnidae and related taxa (Sturnidae sensu lato) remain unresolved due to high rates of morphological change and concomitant morphological homoplasy. This study presents five new mitogenomes of Sturnidae sensu lato and comprehensive mitogenomic analyses. The investigated mitogenomes exhibit an identical gene composition of 37 genes-including 13 protein-coding genes (PCGs), 2 rRNA genes, and 22 tRNA genes-and one control region (CR). The most important finding of this study is drawn from CAM analyses. The surprisingly unique motifs for each species provide a new direction for the molecular species identification of avian. Furthermore, the pervasiveness of the natural selection of PCGs is found in all examined species when analyzing their nucleotide composition and codon usage. We also determine the structures of mt-tRNA, mt-rRNA, and CR structures of Sturnidae sensu lato. Lastly, our phylogenetic analyses not only well support the monophyly of Sturnidae, Mimidae, and Buphagidae, but also define nine stable subclades. Taken together, our findings will enable the further elucidation of the evolutionary relationships within Sturnidae sensu lato.

Explainability increases trust resilience in intelligent agents.

Even though artificial intelligence (AI)-based systems typically outperform human decision-makers, they are not immune to errors, leading users to lose trust in them and be less likely to use them again-a phenomenon known as algorithm aversion. The purpose of the present research was to investigate whether explainable AI (XAI) could function as a viable strategy to counter algorithm aversion. We conducted two experiments to examine how XAI influences users' willingness to continue using AI-based systems when these systems exhibit errors. The results showed that, following the observation of algorithms erring, the inclination of users to delegate decisions to or follow advice from intelligent agents significantly decreased compared to the period before the errors were revealed. However, the explainability effectively mitigated this decline, with users in the XAI condition being more likely to continue utilizing intelligent agents for subsequent tasks after seeing algorithms erring than those in the non-XAI condition. We further found that the explainability could reduce users' decision regret, and the decrease in decision regret mediated the relationship between the explainability and re-use behaviour. These findings underscore the adaptive function of XAI in alleviating negative user experiences and maintaining user trust in the context of imperfect AI.

Running-based food aversion learning in freely-fed and hydrated rats: Daily monitoring of running-induced nausea by measuring kaolin clay ingestion.

The main objective of this research was to demonstrate food aversion learning in rats with unrestricted access to food and water, using wheel running as the unconditioned stimulus. Experiment 1 showed that the target-running paired training group consumed a statistically smaller amount of the target food (tteok rice cakes) compared to the target/running unpaired control group, but the decrease in consumption over days in the paired group was not fully supported by a statistical test. Experiment 2a improved the methodology by familiarizing rats with tteok before training, which resulted in both a statistically significant group effect and a statistically significant daily decrease in tteok consumption. Experiment 2b demonstrated that tteok aversion could be reacquired after an extinction phase. These experiments indicate that running-based tteok aversion in non-deprived rats is a valid example of Pavlovian conditioning and suggest that wheel running can cause similar effects in unrestricted rats as observed in food- or water-restricted rats. Additionally, daily measurements of kaolin clay ingestion suggested that wheel running induced nausea in the rats of these experiments.

The Orbitofrontal Cortex Is Required for Learned Modulation of Innate Olfactory Behavior.

Animals have evolved innate responses to cues including social, food, and predator odors. In the natural environment, animals are faced with choices that involve balancing risk and reward where innate significance may be at odds with internal need. The ability to update the value of a cue through learning is essential for navigating changing and uncertain environments. However, the mechanisms involved in this modulation are not well defined in mammals. We have established a new olfactory assay that challenges a thirsty mouse to choose an aversive odor over an attractive odor in foraging for water, thus overriding their innate behavioral response to odor. Innately, mice prefer the attractive odor port over the aversive odor port. However, decreasing the probability of water at the attractive port leads mice to prefer the aversive port, reflecting a learned override of the innate response to the odors. The orbitofrontal cortex (OFC) is a fourth-order olfactory brain area, involved in flexible value association, with behaviorally relevant outputs throughout the limbic system. We performed optogenetic and chemogenetic silencing experiments that demonstrate the OFC is necessary for this learned modulation of innate aversion to odor. Further, we characterized odor evoked c-fos expression in learned and control mice and found significant suppression of activity in the bed nucleus of the stria terminalis, lateral septum, and central and medial amygdala. These findings reveal that the OFC is necessary for the learned override of innate behavior and may signal to limbic structures to modulate innate response to odor.

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.

BACKGROUND: Src family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively. METHODS: A rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis. RESULTS: SFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1). CONCLUSIONS: In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine.

The apple does not fall far: stable predictive relationships between parents' ratings of their own and their children's self-regulatory abilities.

Having control over your own behavior and impulses is a critical skill that influences children's academic, social, and emotional development. This study investigates the stability and predictive relationships between parents' ratings of their own and their children's executive function and delay aversion. Using data from approximately 1700 families collected during the COVID-19 pandemic, we employed hierarchical structural equation models and cross-lagged panel models to analyze the temporal stability and directional influences of executive function and delay aversion assessments.Our analysis revealed a substantial latent correlation (r = 0.48, p < 0.001) between parents' and children's executive function problems, indicating a shared variance of approximately 23%. Significant cross-lagged effects were found, with parental executive functions at T1 predicting child executive functions at T2 (ß = 0.16, p = 0.005). For delay aversion, we found a latent correlation of r = 0.53 (p < 0.001) and significant within-timepoint and temporal stability, but no cross-lagged effects.These findings suggest that higher levels of executive function problems reported by parents at T1 correspond to an increased perception of similar problems in their children at T2. This highlights the importance of parental self-perception in assessing children's abilities. Our results highlight the importance of incorporating family dynamics into interventions targeting executive function difficulties and delay aversion in children, and understanding this interplay enables the development of more effective, individualized approaches to support positive developmental outcomes.

Mouse aversion to induction with isoflurane using the drop method.

Isoflurane anesthesia prior to carbon dioxide euthanasia is recognized as a refinement by many guidelines. Facilities lacking access to a vaporizer can use the "drop" method, whereby liquid anesthetic is introduced into an induction chamber. Knowing the least aversive concentration of isoflurane is critical. Previous work has demonstrated that isoflurane administered with the drop method at a concentration of 5% is aversive to mice. Other work has shown that lower concentrations (1.7% to 3.7%) of isoflurane can be used to anesthetize mice with the drop method, but aversion to these concentrations has not been tested. We assessed aversion to these lower isoflurane concentrations administered with the drop method, using a conditioned place aversion (CPA) paradigm. Female C57BL/6J (OT-1) mice (n = 28) were randomly allocated to one of three isoflurane concentrations: 1.7%, 2.7%, and 3.7%. Mice were acclimated to a light-dark apparatus. Prior to and following dark (+ isoflurane) and light chamber conditioning sessions, mice underwent an initial and final preference assessment; the change in the duration spent within the dark chamber between the initial and final preference tests was used to calculate a CPA score. Aversion increased with increasing isoflurane concentration: from 1.7% to 2.7% to 3.7% isoflurane, mean ± SE CPA score decreased from 19.6 ± 20.1 s to -25.6 ± 23.2 s, to -116.9 ± 30.6 s (F1,54 = 15.4, p < 0.001). Our results suggest that, when using the drop method to administer isoflurane, concentrations between 1.7% and 2.7% can be used to minimize female mouse aversion to induction.

The acceptability of the risk of death in the treatment of respiratory diseases in France.

BACKGROUND: The costs associated with respiratory illnesses in the French healthcare budget continue to rise. However, pharmaceutical companies and research centres are continuously developing new treatments. Consequently, accepting these treatments, which necessitates the acceptance of the mortality risk associated with their use, represents a significant economic and public health issue. Our study aims to assess this acceptance. METHODS: The data were obtained from an online questionnaire completed by 315 respondents located in France during June and July 2019. The standard gamble method was employed to ascertain the acceptability of risk. This method quantifies the 'disutility' of a health state by evaluating the extent to which an individual is willing to accept a specific mortality risk in exchange for avoiding the state. RESULTS: The study demonstrated that individuals, irrespective of their personal characteristics, were willing to accept a treatment with an average mortality risk of less than 19%. The findings revealed discrepancies between individuals' perceptions of mortality and actual risks. CONCLUSIONS: In France, it is incumbent upon public decision-makers and research centres to ensure that treatment-related mortality rates remain below 19% so that patients readily accept treatment, irrespective of their personal characteristics. In addition, they should provide further information on the risks associated with treating respiratory diseases to avoid a discrepancy between the mortality risks perceived by individuals and the actual risks.

Negative performance feedback from algorithms or humans? effect of medical researchers' algorithm aversion on scientific misconduct.

Institutions are increasingly employing algorithms to provide performance feedback to individuals by tracking productivity, conducting performance appraisals, and developing improvement plans, compared to traditional human managers. However, this shift has provoked considerable debate over the effectiveness and fairness of algorithmic feedback. This study investigates the effects of negative performance feedback (NPF) on the attitudes, cognition and behavior of medical researchers, comparing NPF from algorithms versus humans. Two scenario-based experimental studies were conducted with a total sample of 660 medical researchers (algorithm group: N1 = 411; human group: N2 = 249). Study 1 analyzes the differences in scientific misconduct, moral disengagement, and algorithmic attitudes between the two sources of NPF. The findings reveal that NPF from algorithms shows higher levels of moral disengagement, scientific misconduct, and negative attitudes towards algorithms compared to NPF from humans. Study 2, grounded in trait activation theory, investigates how NPF from algorithms triggers individual's egoism and algorithm aversion, potentially leading to moral disengagement and scientific misconduct. Results indicate that algorithm aversion triggers individuals' egoism, and their interaction enhances moral disengagement, which in turn leads to increased scientific misconduct among researchers. This relationship is also moderated by algorithmic transparency. The study concludes that while algorithms can streamline performance evaluations, they pose significant risks to scientific misconduct of researchers if not properly designed. These findings extend our understanding of NPF by highlighting the emotional and cognitive challenges algorithms face in decision-making processes, while also underscoring the importance of balancing technological efficiency with moral considerations to promote a healthy research environment. Moreover, managerial implications include integrating human oversight in algorithmic NPF processes and enhancing transparency and fairness to mitigate negative impacts on medical researchers' attitudes and behaviors.

Electroacupuncture inhibited carrageenan-induced pain aversion by activating GABAergic neurons in the ACC.

Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.

Inequality aversion predicts support for public and private redistribution.

Rising inequality has brought redistribution back on the political agenda. In theory, inequality aversion drives people's support for redistribution. People can dislike both advantageous inequality (comparison relative to those worse off) and disadvantageous inequality (comparison relative to those better off). Existing experimental evidence reveals substantial variation across people in these preferences. However, evidence is scarce on the broader role of these two distinct forms of inequality aversion for redistribution in society. We provide evidence by exploiting a unique combination of data. We use an incentivized experiment to measure inequality aversion in a large population sample (≈9,000 among 20- to 64-y-old Danes). We link the elicited inequality aversion to survey information on individuals' support for public redistribution (policies that reduce income differences) and administrative records revealing their private redistribution (real-life donations to charity). In addition, the link to administrative data enables us to include a large battery of controls in the empirical analysis. Theory predicts that support for public redistribution increases with both types of inequality aversion, while private redistribution should increase with advantageous inequality aversion, but decrease with disadvantageous inequality aversion. A strong dislike for disadvantageous inequality makes people willing to sacrifice own income to reduce the income of people who are better off, thereby reducing the distance to people with more income than themselves. Public redistribution schemes achieve this but private donations to charity do not. Our empirical results provide strong support for these predictions and with quantitatively large effects compared to other predictors.

War exposure and changes in eating behaviours in Ukrainian school-aged children: A cross-sectional online survey.

The war in Ukraine has exposed children to extremely high levels of acute and chronic stressors, which can impact their eating behaviour (EB). We aimed to determine the prevalence of war-induced, stress-related disruptions in EB of Ukrainian children. We conducted a cross-sectional online survey among parents of 5- to 17-year-old children, who had experienced the war in Ukraine in February-May 2023. Guardians reported their child's various war exposure changes in EBs using a modified version of the Child Eating Behaviour Questionnaire. We assessed associations between total and medium-term EB changes and age, sex, and war exposure using bivariate correlations and χ2 tests. Logistic regression models were fitted to explore the associations between socio-demographic factors, war exposure and frequency of EB changes. Of the 4854 children, 63% had changes in EBs during the war. The most common EB changes included food cravings (38%), food fussiness (37%), and aversion to certain foods (29%). Of the reported EB changes, 40% were medium-term, lasting over a month, and related to altered attitudes towards food. Food insecurity (adjusted OR 2.35, 95% CI: 1.76-3.14), and displacement (internally 2.01, 1.19-3.42) emerged as the most influential determinants of medium-term EB changes. The findings underscore a significant and robust association between war-related exposures and an increased risk of frequent EB changes. As healthy EBs are learned during childhood and have been shown to track into adulthood, the identified disruptions in EB may have medium-term consequences for the physical and mental health of Ukrainian children.

UPRER-immunity axis acts as physiological food evaluation system that promotes aversion behavior in sensing low-quality food.

To survive in challenging environments, animals must develop a system to assess food quality and adjust their feeding behavior accordingly. However, the mechanisms that regulate this chronic physiological food evaluation system, which monitors specific nutrients from ingested food and influences food-response behavior, are still not fully understood. Here, we established a low-quality food evaluation assay system and found that heat-killed E. coli (HK-E. coli), a low-sugar food, triggers cellular UPRER and immune response. This encourages animals to avoid low-quality food. The physiological system for evaluating low-quality food depends on the UPRER (IRE-1/XBP-1) - Innate immunity (PMK-1/p38 MAPK) axis, particularly its neuronal function, which subsequently regulates feeding behaviors. Moreover, animals can adapt to a low-quality food environment through sugar supplementation, which inhibits the UPRER -PMK-1 regulated stress response by increasing vitamin C biosynthesis. This study reveals the role of the cellular stress response pathway as physiological food evaluation system for assessing nutritional deficiencies in food, thereby enhancing survival in natural environments.

We quickly learn to steer clear of eating the moldy apple, the foul-smelling piece of chicken or the leftovers that taste a little 'off'. This survival instinct is shared across most animal species ­ even those with extremely simple and limited visual or taste systems, like the tiny worm Caenorhabditis elegans. Indeed, assessing the safety and quality of available food items can also rely on cells activating built-in cascades of molecular reactions. However, it remains unclear how these 'cellular stress response programs' actually help guide feeding behaviors. To better understand this process, Liu et al. conducted a series of experiments using C. elegans worms exposed to heat-killed bacteria, which are devoid of many nutrients essential for growth. After initially consuming these bacteria, the worms quickly started to avoid feeding on this type of low-quality food. This suggests that mechanisms occurring after ingestion allowed the worms to adjust their feeding choices. Further work showed that the consumption of heat-killed bacteria triggered two essential stress response pathways, known as the unfolded protein response and the innate immune response. The activation of these pathways was essential for the animals to be able to change their behavior and avoid the heat-killed bacteria. These biochemical pathways were particularly active in the worms' nerve cells, highlighting the importance of these cells in sensing and reacting to food. Finally, Liu et al. also found that adding sugars like lactose and sucrose to the low-quality food could prevent the activation of the stress response pathways. This result suggests that specific nutrients play a central role in how these worms decide what to eat. These findings shed light on the complex systems that ensure organisms consume the nutritious food they need to survive. Understanding these processes in worms can provide insights into the broader biological mechanisms that help animals avoid harmful food.

Uncertainty about paternity: a study on deliberate ignorance.

Deliberate ignorance is the willful choice not to know the answer to a question of personal relevance. The question of whether a man is the biological father of his child is a sensitive issue in many cultures and can lead to litigation, divorce, and disinheritance. Thanks to DNA tests, men are easily able to resolve the uncertainty. Psychological theories that picture humans as informavores who are averse to ambiguity suggest men would do a DNA test, as does evolutionary theory, which considers investing in raising a rival's offspring a mistake. We conducted two representative studies using computer-based face-to-face interviews in Germany (n = 969) and Spain (n = 1,002) to investigate whether men actually want to know and how women would react to this desire. As a base line, Germans (Spanish) estimated that 10% (20%) of fathers mistakenly believe that they are the biological father of their child. Nevertheless, in both countries, only 4% of fathers reported that they had performed a DNA paternity test, while 96% said they had not. In contrast, among men without children, 38% (33%) of Germans (Spanish) stated they would do a DNA test if they had children, mostly without telling their partners. Spanish women with children would more often disapprove of a paternity test or threaten their husbands with divorce (25%) than would German women (13%). We find that a simple test of risk aversion, measured also by the purchase of non-mandatory insurances, is correlated with not wanting to know.

Underutilization of Injectable Parkinson's Disease Medication: An Analysis of Neurologist and Patient Perspectives.

BACKGROUND: We hypothesized that many neurologists underestimate patients' willingness to self-administer injectable Parkinson's disease (PD) medication. OBJECTIVE: To evaluate patient and physician perceptions contributing to underutilization of PD medications for acute OFF episodes. ANALYTIC METHOD: Data were collected using an online survey including n = 4063 PD patients experiencing OFF episodes and n = 200 neurologists. RESULTS: 89% of patients were willing to self-inject rescue therapies to treat acute OFF episodes. After reviewing patient survey data, 54% of general neurologists and 37% of movement disorder specialist (MDS) demonstrated a change in perceptions about patients' willingness to use self-injected therapies (P < 0.05). 37% of general neurologists and 21% of MDS indicated a greater likelihood of prescribing these treatments (P < 0.05). CONCLUSIONS: Most patients suffering from OFF episodes would be willing to self-inject to abort their symptoms. Neurologists underestimate this patient acceptance. Understanding patient attitudes and further education about rescue therapies is likely to increase use of these therapies.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

The Importance of Psychological Assessment in the Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Report.

This case report emphasizes the crucial role of psychological assessment in the management of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia. A 48-year-old woman with a five-year history of refractory BPS/IC and vulvodynia presented with frequent urination, pelvic pain, and severe dyspareunia, which led to sexual aversion and divorce from her partner. Previous treatments, including lifestyle modifications, analgesics, anticholinergics, hydrodistension, intravesical dimethyl sulfoxide, and psychiatric interventions, had been ineffective. Psychological assessments using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Toronto Alexithymia Scale-20 revealed severe symptoms of depression, anxiety, and alexithymia. Due to the patient's sexual aversion and the absence of a partner, a complete Female Sexual Function Index (FSFI) could not be administered. Instead, a partial FSFI and artificial intelligence-translated reference value of the Female Sexual Distress Scale-Revised were used to assess aspects relevant to the patient's condition. The patient underwent three monthly sessions of Fotona laser therapy, erbium, and neodymium laser at one-month intervals. Treatment outcomes were evaluated using the Numeric Rating Scale-11, Vulvodynia Total, Interstitial Cystitis Symptom Index, and psychological assessment tools. At the six-month follow-up, all physical and psychological symptoms showed significant improvement and complete remission was achieved at 12 months. Despite the overall positive treatment outcomes, the patient's sexual aversion persisted, and accurate measurement was not possible, highlighting the complexity of addressing sexual function in patients with BPS/IC and vulvodynia. This case report underscores the need for a holistic approach to managing these conditions, addressing both the physical and psychological aspects of the disease.

Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli.

The mesolimbic dopamine (DA) system (MDS) is the canonical "reward" pathway that has been studied extensively in the context of the rewarding properties of sex, food, and drugs of abuse. In contrast, very little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli. Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc) core codes for the salience of social stimuli through the phasic release of DA in response to both rewarding and aversive social stimuli. In contrast, we hypothesize that projections from the lateral VTA to the NAc shell codes for the rewarding properties of social stimuli by increasing the tonic release of DA and the aversive properties of social stimuli by reducing the tonic release of DA. Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA signaling in the NAc core or shell while rewarding and aversive social interactions were taking place. These findings, as well as additional anatomical and functional studies, provide strong support for the proposed neural circuitry underlying the response of the MDS to social stimuli. Together, these data provide a novel conceptualization of how the functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion. Significance Statement: Social interactions of both positive and negative valence are highly salient stimuli that profoundly impact social behavior and social relationships. Although DA projections from the VTA to the NAc are involved in reward and aversion little is known about their role in the saliency and valence of social stimuli. Here, we report that DA projections from the mVTA to the NAc core signal the salience of social stimuli, whereas projections from the lVTA to the NAc shell signal valence of social stimuli. This work extends our current understanding of the role of DA in the MDS by characterizing its subcircuit connectivity and associated function in the processing of rewarding and aversive social stimuli.

Drug discrimination learning: Interoceptive stimulus control of behavior and its implications for regulated and dysregulated drug intake.

Drug discrimination research has generated rich evidence for the capacity of interoceptive drug stimuli to control behavior by serving as discriminative cues. Owing to its neuropharmacological specificity, drug discrimination learning has been widely used to characterize the stimulus effects and neuropharmacological underpinning of drugs. Apart from such utility, discriminative drug stimuli may help regulate drug use by disambiguating conditioned associations and post-intake outcomes. First, this review summarizes the evidence supporting interoceptive regulation of drug intake from the literature of exteroceptive discriminative control of drug-related behavior, effects of drug priming, and self-titration of drug intake. Second, an overview of interoceptive control of reward-seeking and the animal model of discriminated goal-tracking is provided to illustrate interoceptive stimulus control of the initiation and patterning of drug intake. Third, we highlight the importance of interoceptive control of aversion-avoidance in the termination of drug-use episodes and describe the animal model of discriminated taste avoidance that supports such a position. In bridging these discriminative functions of drug stimuli, we propose that interoceptive drug stimuli help regulate intake by disambiguating whether intake will be rewarding, nonrewarding, or aversive. The reflection and discussion on current theoretical formulations of interoceptive control of drug intake may further scientific advances to improve animal models to study the mechanisms by which interoceptive stimuli regulate drug intake, as well as how alterations of interoceptive processes may contribute to the transition to dysregulated drug use.