Intranasal oxytocin enhances the perception of ambiguous averted gaze in women but not in men.

BACKGROUND: Perceiving accurately that others are looking away from us (averted gaze) is as important, for social interactions, as perceiving that others are looking at us (direct gaze). However, previous studies have revealed that when the deflection angle of averted gaze is small, individuals tend to falsely perceive it as direct gaze. Oxytocin (OXT) has been shown to increase orientation to the eye region. Therefore, a critical question is whether and how OXT would facilitate the perception of ambiguous averted gaze. OBJECTIVES: The present study aimed to measure the effects of OXT on the performance of males and females in distinguishing ambiguous averted gaze from direct gaze of different emotional faces. METHODS: In a double-blind placebo-controlled crossover experiment, 48 participants were presented successively two emotional faces with direct gaze (defined as 0, indicating the center of the eye) or averted gaze (defined as ±4, indicating the corner of the eye; +4 means that the iris moves 4 steps to the right; and -4 means that the iris moves 4 steps to the left) following intranasal oxytocin or placebo treatment and asked to make judgments on whether or not the two faces were the same in terms of identity. The interference effect of gaze direction was calculated by subtracting the mean accuracy and reaction time in the congruent gaze condition from those in the incongruent gaze condition. The logic of the measurement was if intranasal OXT would facilitate the detection of ambiguous averted gaze, we would observe a larger interference effect in the gaze incongruent condition compared with the gaze congruent condition, leading to longer RT or/and lower accuracy for identification judgment in the gaze incongruent condition. RESULTS: While there were no OXT effects in accuracy, we found a significant interaction between treatment, sex, and gaze congruency in reaction times. That is, following OXT as compared to placebo, women displayed stronger interference of gaze direction, whereas in men no significant difference was observed. Besides, this interaction did not vary across different emotional expressions. CONCLUSIONS: Our findings provide the first evidence for sex-dependent effects of OXT on the perception of ambiguous averted gaze. Given potential therapeutic applications of OXT to patients with developmental and psychiatric disorders, who are characterized as atypical in encoding gaze features, the findings suggest that rather different treatment outcomes could be anticipated in males and females.

Effects of acetaminophen on risk taking.

Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen's effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden.

Reward and punisher experience alter rodent decision-making in a judgement bias task.

The influence of affective states on decision-making is likely to be complex. Negative states resulting from experience of punishing events have been hypothesised to generate enhanced expectations of future punishment and 'pessimistic'/risk-averse decisions. However, they may also influence how decision-outcomes are valued. Such influences may further depend on whether decisions at hand are germane to the rewards or punishers that induced the affective state in the first place. Here we attempt to dissect these influences by presenting either many or few rewards or punishers of different types (sucrose vs air-puff; 50 kHz vs 22 kHz ultrasonic vocalisations) to rats, and investigating their subsequent decisions in a judgement bias task that employed sucrose and air-puff as decision outcomes. Rats that received many sucrose pellets prior to testing were more risk-averse than those receiving many air-puffs. Ultrasonic vocalisations did not alter decision-making. Computational analysis revealed a higher weighting of punishers relative to rewards (in agreement with findings from a separate behavioural task) and a bias towards the risk-averse response following pre-test sucrose compared to pre-test air-puff. Thus, in this study reward and punisher manipulation of affective state appeared to alter decision-making by influencing both expectation and valuation of decision-outcomes in a domain-specific way.

Oxytocin modulation of self-referential processing is partly replicable and sensitive to oxytocin receptor genotype.

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress towards a therapeutic application of OXT in disorders with social-emotion impairments is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, employing a validated oxytocin-sensitive trait judgment paradigm, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) reduces the self-referential bias in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocin's behavioral effects. We confirmed that in the whole sample oxytocin influenced self-other distinction in terms of reduced decision time. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on subsequent memory performance were only found in rs2268498 TT homozygotes. In summary, the current study partially replicates our previous findings showing that oxytocin reduces the self-referential bias and suggests that sensitivity to its effects in this domain are receptor genotype dependent.

Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment.

RATIONALE: 5-methoxy-N,N-dimethyltryptamine is a psychotropic substance found in various plant and animal species and is synthetically produced. 5-methoxy-N,N-dimethyltryptamine is used in naturalistic settings for spiritual exploration, recreation, or to address negative affect and mood problems. However, scientific knowledge on the effects of 5-methoxy-N,N-dimethyltryptamine in humans is scarce. OBJECTIVES: The first objective was to assess the effects of inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine on neuroendocrine markers. The second objective was to assess effects of the substance on affect and mindfulness. In addition, we assessed whether ratings of subjective measures were associated with changes in stress biomarkers (i.e., cortisol) and immune response (i.e., IL-6, CRP, IL-1ß), as well as the acute psychedelic experience. METHODS: Assessments (baseline, immediately post-session, and 7-day follow-up) were made in 11 participants. Salivary samples were collected at baseline and post-session and analyzed by high-sensitivity enzyme-linked immunosorbent assay (ELISA). RESULTS: 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately post-session. These changes were not correlated to ratings of mental health or the psychedelic experience. Relative to baseline, ratings of non-judgment significantly increased, and ratings of depression decreased immediately post-session and at follow-up. Ratings of anxiety and stress decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with ratings of affect and positively with ratings of non-judgment. CONCLUSION: Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine produced significant changes in inflammatory markers, improved affect, and non-judgment in volunteers. Future research should examine the effect of 5-methoxy-N,N-dimethyltryptamineamine with healthy volunteers in a controlled laboratory setting.

Opposing sex-dependent effects of oxytocin on the perception of gaze direction.

BACKGROUND: Gaze direction is an important cue of the eye region. Previous studies have revealed that oxytocin (OXT) increases orienting to the eye region of face. However, little has been known about the effect of OXT in men and women on the perception of gaze direction particularly when associated with different emotions. OBJECTIVES: We investigated how oxytocin would affect gaze direction judgments for threatening, angry, and neutral facial expressions and whether this effect would be modulated by observers' sex. METHODS: We used the cone of direct gaze (CoDG) task. Participants were required to judge the gaze direction of face between directed and averted gaze. RESULTS: Results showed opposing sex-dependent effects of OXT such that OXT, as compared with placebo, tended to decrease the CoDG in men but increase it in women. The CoDG was marginally wider in men than in women in the placebo condition, and however, this difference was abolished following OXT treatment. We also found that the perception of gaze direction varied as a function of emotional expression such that the CoDG for angry and neutral faces was wider than that for fearful faces and the CoDG for angry faces was marginally wider than that for neutral ones. However, there was no significant interaction between treatment and facial expression. CONCLUSIONS: Our findings provide the first evidence for sex-dependent effects of OXT on gaze direction perception, suggesting that OXT attenuates the self-referential judgment of gaze directions of others in men and enhances it in women despite differentiated emotions of faces.

Oxytocin amplifies the influence of good intentions on social judgments.

Studies have shown that the evolutionarily conserved neuropeptide oxytocin (OT) promotes various prosocial behaviors, yet there are few studies of the effect of OT on social judgments, especially on judgments when the actor's intention and the final outcome are incongruent. In a double-blind, placebo-controlled experiment, participants were asked to play the role of the recipient in a dictator game and to make social judgments about the dictator after intranasal OT administration. To isolate the outcome and the intention of the dictator's allocation, we developed a novel social judgment task in which recipients were told that 50% of the dictators' proposals would be reversed. The results showed that the effect of OT on social judgment was modulated by intention: OT increased goodness ratings only towards dictators with hyperfair intention. Our findings support the affiliative-motivation theory which states that OT enhances the affiliative motivation and recognition of positive-valence social stimuli.

Pharmacological manipulations of judgement bias: A systematic review and meta-analysis.

Validated measures of animal affect are crucial to research spanning numerous disciplines. Judgement bias, which assesses decision-making under ambiguity, is a promising measure of animal affect. One way of validating this measure is to administer drugs with affect-altering properties in humans to non-human animals and determine whether the predicted judgement biases are observed. We conducted a systematic review and meta-analysis using data from 20 published research articles that use this approach, from which 557 effect sizes were extracted. Pharmacological manipulations overall altered judgement bias at the probe cues as predicted. However, there were several moderating factors including the neurobiological target of the drug, whether the drug induced a relatively positive or negative affective state in humans, dosage, and the presented cue. This may partially reflect interference from adverse effects of the drug which should be considered when interpreting results. Thus, the overall pattern of change in animal judgement bias appears to reflect the affect-altering properties of drugs in humans, and hence may be a valuable measure of animal affective valence.

Exogenous testosterone increases sensitivity to moral norms in moral dilemma judgements.

Moral dilemma judgements frequently involve decisions where moral norms and the greater good are in conflict. The current preregistered study tested the effect of the steroid hormone testosterone on moral dilemma judgements using a double-blind administration of testosterone or placebo. Counter to predictions, testosterone administration led to increased inaction in moral dilemmas where harmful actions prohibited by moral norms increase overall well-being. Using a mathematical model to disentangle sensitivity to consequences, sensitivity to moral norms and general preference for inaction versus action, analyses further revealed that testosterone administration influenced judgements by increasing sensitivity to moral norms. Exploratory analyses suggested the opposite pattern for endogenous testosterone measured at baseline, in that higher levels of endogenous testosterone were associated with lower sensitivity to moral norms. The results indicate that the role of testosterone in moral judgements is more complex than suggested by previous findings. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 13 November 2017. The protocol, as accepted by the journal, can be found at https://osf.io/rysbe/ 1.

Alcohol, empathy, and morality: acute effects of alcohol consumption on affective empathy and moral decision-making.

RATIONALE: Hypothetical moral dilemmas, pitting characteristically utilitarian and non-utilitarian outcomes against each other, have played a central role in investigations of moral decision-making. Preferences for utilitarian over non-utilitarian responses have been explained by two contrasting hypotheses; one implicating increased deliberative reasoning, and the other implicating diminished harm aversion. In recent field experiments, these hypotheses have been investigated using alcohol intoxication to impair both social and cognitive functioning. These studies have found increased utilitarian responding, arguably as a result of alcohol impairing affective empathy. OBJECTIVES: The present research expands existing investigations by examining the acute effects of alcohol on affective empathy and subsequent moral judgments in traditional vignettes and moral actions in virtual reality, as well as physiological responses in moral dilemmas. METHODS: Participants (N = 48) were administered either a placebo or alcohol in one of two dosages; low or moderate. Both pre- and post intervention, participants completed a moral action and moral judgment task alongside behavioural measures of affective empathy. RESULTS: Higher dosages of alcohol consumption resulted in inappropriate empathic responses to facial displays of emotion, mirroring responses of individuals high in trait psychopathy, but empathy for pain was unaffected. Whilst affective empathy was influenced by alcohol consumption in a facial responding task, both moral judgments and moral actions were unaffected. CONCLUSIONS: These results suggest that facets, beyond or in addition to deficits in affective empathy, might influence the relationship between alcohol consumption and utilitarian endorsements.

Air Pollution Predicts Harsh Moral Judgment.

The present research recruited participants from China, which is suffering from serious air pollution, and examined whether air pollution would be associated with moral judgment and immoral behavioral intention. Study 1 (n = 145) used the objective Air Quality Index to indicate the level of air pollution and found that it predicted harsh judgment on others' moral violations but did not predict judgment on others' non-moral negative behaviors or their own immoral behavioral intentions. Study 2 (n = 90) asked participants either to recall a past experience of being exposed to air pollution or to recall a neutral experience and consistently found that air pollution only influenced judgment on moral violations. The findings also ruled out the feeling of threat or the trust of government as possible mediators in the relationship between air pollution and harsh moral judgment.

The influence of oxytocin and vasopressin on men's judgments of social dominance and trustworthiness: An fMRI study of neutral faces.

Cues signaling trust and dominance are crucial for social life. Previous studies on the effects of oxytocin (OT) nasal sprays on trustworthiness evaluations have been inconsistent and its influence on dominance is unknown. Vasopressin (AVP) may also influence social cue perception, but even fewer investigations have evaluated this possibility. We evaluated the effects of intranasal OT and AVP compared to placebo control during three double-blinded functional magnetic resonance imaging sessions. Twenty males received a pseudo-randomized order of nasal spray conditions and rated the trustworthiness and dominance of neutral faces. OT increased facial dominance ratings compared to placebo. Neuroimaging results revealed an inverse relationship between brain activation and face ratings for OT compared to placebo in regions involved in processing emotional expressions. Specifically, the right superior temporal gyrus was attenuated as ratings increased and the left precuneus selectively diminished with increasing dominance ratings. Additionally, OT increased functional connectivity between frontoparietal regions and the right amygdala for faces rated as highly dominant, but OT increased connectivity between the fusiform gyrus, hippocampus, and bilateral ventral tegmental area (VTA) for faces perceived as highly trustworthy. Overall, OT increased the perception of dominance but did not influence trustworthiness judgments. However, we observed regional neural effects for OT that differed between judgments of trustworthiness and dominance. AVP attenuated left temporoparietal junction activity as face ratings increased, a result consistent with AVP influencing mentalization. AVP also led to increased left amygdala and right VTA connectivity with the putamen, which is consistent with cue-driven, habitual responses.

How perceived substance characteristics affect ethical judgement towards cognitive enhancement.

Some individuals seek to enhance their cognitive capabilities through the use of pharmacology. Such behavior entails potential health risks and raises ethical concerns. The aim of this study was to examine whether a precursor of behavior, ethical judgement towards the use of existing biological cognitive enhancers (e.g., coffee, legal and illegal drugs), is shaped by the perceived characteristics of these cognitive enhancers. Students and employees completed an online questionnaire which measured perceived characteristics of 15 substances presented as potential cognitive enhancers and a measure of ethical judgement towards these cognitive enhancers. Results of mixed model regression analyzes show that ethical judgement is more favourable when cognitive enhancers are perceived as being legal, familiar, efficient, and safe for users' health, supporting all hypotheses. Results further show that 36% of variance (in the null model) lies at the level of cognitive enhancers and 21% at the level of participants. In conclusion, cognitive enhancers vary widely in terms of ethical judgement, which is explained by the perception of the mentioned characteristics. Implications regarding prevention and policy-making are discussed.

Methylphenidate modifies activity in the prefrontal and parietal cortex accelerating the time judgment.

Methylphenidate produces its effects via actions on cortical areas involved with attention and working memory, which have a direct role in time estimation judgment tasks. In particular, the prefrontal and parietal cortex has been the target of several studies to understand the effect of methylphenidate on executive functions and time interval perception. However, it has not yet been studied whether acute administration of methylphenidate influences performance in time estimation task and the changes in alpha band absolute power in the prefrontal and parietal cortex. The current study investigates the influence of the acute use of methylphenidate in both performance and judgment in the time estimation interpretation through the alpha band absolute power activity in the prefrontal and parietal cortex. This is a double-blind, crossover study with a sample of 32 subjects under control (placebo) and experimental (methylphenidate) conditions with absolute alpha band power analysis during a time estimation task. We observed that methylphenidate does not influence task performance (p > 0.05), but it increases the time interval underestimation by over 7 s (p < 0.001) with a concomitant decrease in absolute alpha band power in the ventrolateral prefrontal cortex and dorsolateral prefrontal cortex and parietal cortex (p < 0.001). Acute use of methylphenidate increases the time interval underestimation, consistent with reduced accuracy of the internal clock mechanisms. Furthermore, acute use of methylphenidate influences the absolute alpha band power over the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, and parietal cortex.

Effects of cognitive judgement bias and acute antidepressant treatment on sensitivity to feedback and cognitive flexibility in the rat version of the probabilistic reversal-learning test.

Depressive disorders are often associated with cognitive biases. In this study, we investigated, in an animal model, whether cognitive judgement bias, measured as a stable and enduring behavioural trait, could modulate the effects of antidepressant drugs on other cognitive processes associated with depression. For this purpose, we identified rats displaying 'pessimistic' and 'optimistic' traits in a series of ambiguous-cue interpretation (ACI) tests. Subsequently, in the preclinical version of the probabilistic reversal-learning (PRL) test, allowing multiple reversals within a test session, we compared the effects of acute administration of 5 different antidepressant (AD) drugs (agomelatine, escitalopram, clomipramine, mirtazapine and venlafaxine) on cognitive flexibility and sensitivity to positive/negative feedback in optimistic and pessimistic animals. We report that, following acute treatment with agomelatine, the proportion of lose-shift behaviours in the PRL test was significantly reduced in pessimistic animals compared to optimists. We also demonstrate that acute treatment with another antidepressant drug, mirtazapine, significantly increased the sensitivity of rats to positive feedback, as indexed by the increased proportion of win-stay behaviour following probabilistic reward. This effect was independent of cognitive bias and was associated with a reduced number of reversals made by the animals. Three other tested drugs had no significant effects on behavioural measures assessed in our study.

Intranasal oxytocin does not alter initial perceptions of facial trustworthiness in younger or older adults.

BACKGROUND: Oxytocin is a neuropeptide involved in a range of social processes, and prior research has shown that intranasal oxytocin (iOT) may enhance trusting behaviors. However, it is unclear whether iOT influences perceptions of whether a face is trustworthy. In addition, no studies in this literature have investigated whether the participant's age may play a moderating role in the effects of iOT on trust. AIMS: We aimed to examine for the first time whether iOT influences perceptions of facial trustworthiness and eye-gaze patterns and, if so, whether age moderates these iOT effects. METHODS: One hundred and eighteen participants took part in a randomized, double-blind, placebo-controlled, within-groups study. Participants made judgments about the perceived trustworthiness of a series of faces while their eye movements were monitored. RESULTS: Younger and older adults differed in their judgments of facial trustworthiness. However, most critically, iOT had no effect on these judgments for either age group. For the eye-tracking data, prior age effects in attending to the stimuli were replicated, with older adults gazing less at the eye region and more at the mouth region relative to younger adults. However, iOT had no effect on eye gaze. CONCLUSIONS: These findings are discussed in relation to the growing body of literature that suggests that the effect of iOT on social processing is complex and may not be as robust as first thought.

"Lie to me"-Oxytocin impairs lie detection between sexes.

The hormone oxytocin modulates various aspects of social behaviors and even seems to lead to a tendency for gullibility. The aim of the current study was to investigate the effect of oxytocin on lie detection. We hypothesized that people under oxytocin would be particularly susceptible to lies told by people of the opposite sex. After administration of oxytocin or a placebo, male and female participants were asked to judge the veracity of statements from same- vs. other-sex actors who either lied or told the truth. Results showed that oxytocin decreased the ability of both male and female participants to correctly classify other-sex statements as truths or lies compared to placebo. This effect was based on a lower ability to detect lies and not a stronger bias to regard truth statements as false. Revealing a new effect of oxytocin, the findings may support assumptions about the hormone working as a catalyst for social adaption.

The Effect of Attention-Deficit/Hyperactivity Disorder and Methylphenidate Treatment on the Adult Auditory Temporal Order Judgment Threshold.

Purpose: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition notes that attention-deficit/hyperactivity disorder (ADHD) diagnosed in childhood will persist into adulthood among at least some individuals. There is a paucity of evidence, however, regarding whether other difficulties that often accompany childhood ADHD will also continue into adulthood, specifically auditory processing deficits. The aim of this study was to examine the effect of ADHD and the stimulant medication methylphenidate on auditory perception performance among adults. Method: A total of 33 adults diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria (ADHD group) and 48 adults without ADHD (non-ADHD group) performed an auditory temporal order judgment task. Participants with ADHD performed the task twice: with and without taking methylphenidate (Ritalin), in random order. Results: Temporal order judgment thresholds of the ADHD group were significantly higher than those of the non-ADHD group. Methylphenidate significantly decreased temporal order judgment thresholds within the ADHD group, making their performance similar to the non-ADHD participants. Conclusions: Auditory processing difficulties of those diagnosed with ADHD seem to persist into adulthood. Similar to findings with children, methylphenidate treatment improves performance on tasks requiring this ability among adults. Therefore, given the association between auditory temporal processing and linguistic skills, the beneficial effect of methylphenidate on adults' academic achievement may be accomplished by positively affecting auditory temporal processing. Further studies in this line of research are needed.

Caffeine cravings impair memory and metacognition.

Cravings for food and other substances can impair cognition. We extended previous research by testing the effects of caffeine cravings on cued-recall and recognition memory tasks, and on the accuracy of judgements of learning (JOLs; predicted future recall) and feeling-of-knowing (FOK; predicted future recognition for items that cannot be recalled). Participants (N = 55) studied word pairs (POND-BOOK) and completed a cued-recall test and a recognition test. Participants made JOLs prior to the cued-recall test and FOK judgements prior to the recognition test. Participants were randomly allocated to a craving or control condition; we manipulated caffeine cravings via a combination of abstinence, cue exposure, and imagery. Cravings impaired memory performance on the cued-recall and recognition tasks. Cravings also impaired resolution (the ability to distinguish items that would be remembered from those that would not) for FOK judgements but not JOLs, and reduced calibration (correspondence between predicted and actual accuracy) for JOLs but not FOK judgements. Additional analysis of the cued-recall data suggested that cravings also reduced participants' ability to monitor the likely accuracy of answers during the cued-recall test. These findings add to prior research demonstrating that memory strength manipulations have systematically different effects on different types of metacognitive judgements.

Serotonin depletion induces pessimistic-like behavior in a cognitive bias paradigm in pigs.

Cognitive and affective processes are highly interrelated. This has implications for neuropsychiatric disorders such as major depressive disorder in humans but also for the welfare of non-human animals. The brain serotonergic system might play a key role in mediating the relationship between cognitive functions and affective regulation. The aim of our study was to examine the influence of serotonin depletion on the affective state and cognitive processing in pigs, an important farm animal species but also a potential model species for biomedical research in humans. For this purpose, we modified a serotonin depletion model using para-chlorophenylalanine (pCPA) to decrease serotonin levels in brain areas involved in cognitive and affective processing (part 1). The consequences of serotonin depletion were then measured in two behavioral tests (part 2): the spatial judgement task (SJT), providing information about the effects of the affective state on cognitive processing, and the open field/novel object (OFNO) test, which measures behavioral reactions to novelty that are assumed to reflect affective state. In part 1, 40 pigs were treated with either pCPA or saline for six consecutive days. Serotonin levels were assessed in seven different brain regions 4, 5, 6, 11 and 13days after the first injection. Serotonin was significantly depleted in all analyzed brain regions up to 13days after the first application. In part 2, the pCPA model was applied to 48 animals in behavioral testing. Behavioral tests, the OFNO test and the SJT, were conducted both before and after pCPA/saline injections. While results from the OFNO tests were inconclusive, an effect of treatment as well as an effect of the phase (before and after treatment) was observed in the SJT. Animals treated with pCPA showed more pessimistic-like behavior, suggesting a more negative affective state due to serotonin depletion. Thus, our results confirm that the serotonergic system is a key player in cognitive-emotional processing. Hence, the serotonin depletion model and the spatial judgement task can increase our understanding of the basic mechanisms underlying both human neuropsychiatric disorders and animal welfare.