Many non-human primates have been observed to reciprocate and to understand reciprocity in one-to-one social exchanges. A recent study demonstrated that capuchin monkeys are sensitive to both third-party reciprocity and violation of reciprocity; however, whether this sensitivity is a function of general intelligence, evidenced by their larger brain size relative to other primates, remains unclear. We hypothesized that highly pro-social primates, even with a relatively smaller brain, would be sensitive to others' reciprocity. Here, we show that common marmosets discriminated between human actors who reciprocated in social exchanges with others and those who did not. Monkeys accepted rewards less frequently from non-reciprocators than they did from reciprocators when the non-reciprocators had retained all food items, but they accepted rewards from both actors equally when they had observed reciprocal exchange between the actors. These results suggest that mechanisms to detect unfair reciprocity in third-party social exchanges do not require domain-general higher cognitive ability based on proportionally larger brains, but rather emerge from the cooperative and pro-social tendencies of species, and thereby suggest this ability evolved in multiple primate lineages.

A camptothecin derivative, irinotecan (Cpt‐11), is a topoisomerase I inhibitor and has a strong activity against a broad range of human cancer. One of the side‐effects of this drug is diarrhoea. Here, we tried to determine the mediator of the irinotecan‐induced Cl− secretion which may underlie this diarrhoea, using isolated mucosae of rat distal colon. Irinotecan increased Cl− secretory current in a concentration‐dependent manner across the mucosa, set between Ussing chambers. Thromboxane A2 (TXA2) has not been reported to date as a physiological stimulant of Cl− secretion in the distal colon. However, the major part of the present irinotecan‐induced current was inhibited by selective thromboxane A2 receptor antagonists (KW‐3635 and ONO‐3708), and a selective thromboxane synthase inhibitor (Y‐20811). In fact, we found that irinotecan stimulated the release of TXA2 in a concentration‐dependent manner from the isolated mucosa into the bathing solutions. Furthermore, 9,11‐epithio‐11,12‐methano‐thromboxane A2 (STA2), a stable analogue of TXA2, induced Cl− secretion, which was almost completely inhibited by the TXA2 receptor antagonists. In single cells of isolated crypts, STA2 depolarized the cell and increased the membrane conductance, indicating that STA2 opened the apical Cl− channel of the crypt cells. We conclude, therefore, that the irinotecan‐induced endogenous TXA2 is a novel stimulant of the Cl− secretion from the crypt cells of distal colon.

Humans and various nonhuman primates respond negatively to inequity not in their favor (i.e., inequity aversion), when inequity between two individuals is introduced. Common marmosets, a highly prosocial species, further discriminated between human actors who reciprocated in social exchanges, and those who did not. Conversely, marmoset models of autism, induced via prenatal exposure to valproic acid (VPA marmosets), did not discriminate. Interestingly, previous studies of inequity aversion in marmosets have produced negative results, or were limited to males. Recent studies suggest that inequity aversion is highly influenced by the tasks employed. Here we show inequity aversion in both male and female marmosets using a novel task which required a relatively long duration of response. Marmosets were required to hold a spoon for 2 s to receive a reward. Marmosets successfully performed the task when they observed an unfamiliar conspecific partner obtaining the same reward (equity test). However, when they witnessed the partner receiving a more attractive reward for equal effort (inequity test), unexposed marmosets, which were not exposed to either valproic acid or saline during the fetal period refused to respond. This inequity aversion was not observed in unexposed marmosets when the partner was absent.　In contrast, marmosets with fetal exposure to valproic acid (VPA marmosets) successfully executed the task irrespective of their partners' reward conditions. As prenatal exposure to valproic acid is a well-known procedure to induce autism spectrum disorder (ASD)-like behaviors in rodents, we propose that VPA marmosets failed to show inequity aversion due to weak social motivation or interest towards others.

No abstract

Reciprocity and cooperation are fundamental to human society and are observed in nonhuman primates. Primates are not only sensitive to direct reciprocity and its violation but also indirect reciprocity. Recent studies demonstrated that some primate species adjusted their behavior by observing others' interactions. Capuchin, marmoset, and squirrel monkeys avoided taking food from human actors who behaved nonreciprocally; however, no such empirical evidence among Old World monkeys is available. Here, we show that common marmosets, which are a highly prosocial species, discriminated between human actors who reciprocated in social exchanges and those who did not; however, Japanese monkeys, who are renowned for despotic social relationships, did not. In the reciprocal condition, 2 human actors exchanged food equally, whereas in the nonreciprocal condition, 1 actor (nonreciprocator) ended up with all the food and the other actor with none. The common marmosets avoided receiving food from the nonreciprocator in the nonreciprocal condition. Nevertheless, the Japanese monkeys did not show differential preferences in either condition. These results suggest a crucial role for prosocial tendencies in monkeys' responses to asymmetric exchanges and indicate that third-party social evaluations are not homologous among primates. Further comparative studies with direct comparisons will be required to explore the underlying mechanism of third-party social evaluations.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication impairments and restricted and repetitive behavior. Although there is currently no established cure for ASD, early interventions for deficits of attention to other individuals are expected to reduce the progression of ASD symptoms in later life. To confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze toward other conspecifics during childhood and puberty in a three-chamber test setting using an ASD marmoset model produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in adult VPA-exposed marmosets as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and that mature animals persisted with previous strategies that required long days for acquisition to pass the test. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are consistent from childhood to adulthood, VPA-exposed marmosets will provide a valuable means of elucidating mechanisms for early intervention and contribute to the development of early therapies.

Individuals with autism spectrum disorder (ASD) are exposed to a variety of stressors owing to their behavioral traits. Cortisol is a hormone typically associated with stress, and its concentration and response to stress are higher in individuals with ASD than in controls. The mechanisms underlying cortisol dysregulation in ASD have been explored in rodents. Although rodent models have successfully replicated the major symptoms of autism (i.e., impaired vocal communication, social interaction deficits, and restricted/repetitive patterns of behavior), evidence suggests that the hypothalamic-pituitary-adrenal (HPA) axis system differs between rodents and primates. We developed an ASD model in the common marmoset (Callithrix jacchus), a New World monkey, utilizing prenatal exposure to valproic acid (VPA). In this study, we collected the salivary cortisol levels in VPA-exposed and unexposed marmosets in the morning and afternoon. Our results revealed that both VPA-exposed and unexposed marmosets showed similar diurnal changes in cortisol levels, which were lower in the afternoon than in the morning. However, heightened cortisol levels were observed throughout the day in VPA-exposed marmosets. These results are consistent with those of ASD in humans. Our results suggest that VPA-exposed marmosets show similarities not only in their behavioral patterns and brain pathologies, which we have reported previously, but also in hormonal regulation, validating the usefulness of VPA-exposed marmosets also as a tool for ASD stress research.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments and restricted and repetitive behavior. Although currently no established cure exists for ASD, early intervention to the deficits of attention to other individuals is expected to reduce the progression of ASD symptoms in later life. In order to confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze towards other conspecifics during childhood and puberty in a three-chamber test setting using an ASD model of marmoset produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in an adult VPA-exposed marmoset as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and adults displayed rigidity of response. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are coherent from childhood to adulthood, VPA-exposed marmosets will provide a valuable opportunity to elucidate mechanisms for early intervention and contribute to the development of early therapies.