Abstract
Disgust can be thought of as an affective system that has evolved to detect signs of pathogens, parasite and toxins as well as to stimulate behaviors that reduce the risk of their acquisition. Disgust incorporates social cognitive mechanisms to regulate exposure to and, or anticipate and avoid exposure to pathogens and toxins. Social cognition entails the acquisition of social information about others (ie, social recognition) and from others (ie, social learning). This involves recognizing and assessing other individuals and the pathogen/parasite/contamination/toxin threat they pose and deciding about when and how to interact with and, or avoid them. Social cognition provides a frame-work for examining the expression of disgust and the associated neurobiological mechanisms. Here, we briefly consider the relations between social cognition and pathogen/parasite/toxin avoidance behaviors. We briefly discuss aspects of: (1) the odor mediated social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on disgust mate and social partner choice; (2) the roles of "out-groups" (strangers, unfamiliar individuals) and "in-groups" (familiar individuals) in the expression of disgust and pathogen avoidance behaviors; (3) individual and social learning of disgust and empathy for disgust; (4) toxin elicited disgust and anticipatory disgust; (5) the neurobiological mechanisms, and in particular the roles of the nonapeptide, oxytocin and estrogenic mechanism associated with social cognition and the expression of disgust. These findings on the social neuroscience of disgust have a direct bearing on our understanding of the roles of disgust in shaping human and nonhuman social behavior. what social groups we adhere to and support, how we select what we eat, the clothing we wear, the music we listen to and likely our concepts of morality.
Abstract
1,2 However, before examining the social neuroscience of disgust it is important to be clear about the term disgust.
Abstract
From an evolutionary perspective disgust responses play a pivotal role in the avoidance of pathogens, contaminants and toxins. Darwin's 3 definition of disgust as "a sensation … referring to something revolting, primarily in relation to the sense of taste, as actually perceived or vividly imagined; and secondarily to anything which causes a similar feeling, through the sense of smell, touch and even eyesight" vividly captures this.
Abstract
Disgust can be considered as a "motivational system" that evolved to detect sign of pathogens, parasites and other infectious agents, along with that of toxins and other contaminants, as well as to stimulate avoidance behaviors that reduce the risk of their acquisition 2, 4 . Cross phyla examples include the avoidance of infected conspecifics in lobsters, fishes, rodents and humans, of pathogenic wastes in nematodes and kangaroos, and hygienic behavior in insects and birds 2,4,5 .
Abstract
Disgust also incorporate nausea/emesis as well as loss of and, or suppression of appetite, all of which contribute to riding the body of toxins and pathogens that have already been either ingested or to decrease the probability of their ingestion. 2, 6, 7 It has been speculated where to copy the behavior of others rather than learning asocially, as well as whose behavior and affective (emotional) states to copy. The degree to which social learning is used depends on the opportunities for social interaction, the extent to which behavior needs to be adjusted to changing social and environmental conditions, and how risky or costly it is to learn asocially. Social information about potential pathogen threat in the absence of any behavioral interactions can also lead to significant emotional, motivational and neurobiological responses affecting the expression

Disgust can be thought of as an affective system that has evolved to detect signs of pathogens, parasite and toxins as well as to stimulate behaviors that reduce the risk of their acquisition. Disgust incorporates social cognitive mechanisms to regulate exposure to and, or anticipate and avoid exposure to pathogens and toxins. Social cognition entails the acquisition of social information about others (ie, social recognition) and from others (ie, social learning). This involves recognizing and assessing other individuals and the pathogen/parasite/contamination/toxin threat they pose and deciding about when and how to interact with and, or avoid them. Social cognition provides a frame-work for examining the expression of disgust and the associated neurobiological mechanisms. Here, we briefly consider the relations between social cognition and pathogen/parasite/toxin avoidance behaviors. We briefly discuss aspects of: (1) the odor mediated social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on disgust mate and social partner choice; (2) the roles of "out-groups" (strangers, unfamiliar individuals) and "in-groups" (familiar individuals) in the expression of disgust and pathogen avoidance behaviors; (3) individual and social learning of disgust and empathy for disgust; (4) toxin elicited disgust and anticipatory disgust; (5) the neurobiological mechanisms, and in particular the roles of the nonapeptide, oxytocin and estrogenic mechanism associated with social cognition and the expression of disgust. These findings on the social neuroscience of disgust have a direct bearing on our understanding of the roles of disgust in shaping human and nonhuman social behavior. what social groups we adhere to and support, how we select what we eat, the clothing we wear, the music we listen to and likely our concepts of morality. 1, 2 However, before examining the social neuroscience of disgust it is important to be clear about the term disgust.

From an evolutionary perspective disgust responses play a pivotal role in the avoidance of pathogens, contaminants and toxins. Darwin's 3 definition of disgust as "a sensation … referring to something revolting, primarily in relation to the sense of taste, as actually perceived or vividly imagined; and secondarily to anything which causes a similar feeling, through the sense of smell, touch and even eyesight" vividly captures this.

Disgust can be considered as a "motivational system" that evolved to detect sign of pathogens, parasites and other infectious agents, along with that of toxins and other contaminants, as well as to stimulate avoidance behaviors that reduce the risk of their acquisition 2, 4 . Cross phyla examples include the avoidance of infected conspecifics in lobsters, fishes, rodents and humans, of pathogenic wastes in nematodes and kangaroos, and hygienic behavior in insects and birds 2, 4, 5 .

Disgust also incorporate nausea/emesis as well as loss of and, or suppression of appetite, all of which contribute to riding the body of toxins and pathogens that have already been either ingested or to decrease the probability of their ingestion. 2, 6, 7 It has been speculated that disgust arose from a basic system of distaste to bitter substances, which functions to void the mouth of toxins, to more complex behavioral responses including the capability to learn vicariously what social and non-social environmental stimuli might present increased risk of contamination and infection. 2 During human social evolution disgust's role is proposed to have extended to moral disgust providing a basis for punishing antisocial behavior and breakers of social norms. 1 This is reflected by the fact that colloquially we refer to disgusting events leaving a bitter taste in our mouth and the findings that physical disgust induced via a bitter taste elicits moral disgust.

Social factors have a key role in pathogen and toxin detection and avoidance, with it early on being hypothesized that various aspects of primate social behavior evolved to reduce the spread of new and existing parasites and pathogens. 8 This involves social cognition and the acquisition and use of social information either actively coming as direct signals from others (eg, alarm calls), or arising indirectly as passive cues or by-products of the behavior and decisions of others with similar needs, requirements, and facing common threats (eg, act of fleeing, metabolic excretions and odors indicating presence and condition). 4, 9 Social cognition which is defined as the processes by which animals acquire, process, retain and act on various forms of social information, 10 involves both the acquisition of information about others (ie, social recognition) and information from others (ie, social learning) combined with the processing and use of that information in decision making and expression of subsequent approach/avoidance and associated behavioral responses. 11 This involves the use of various sensory modalities to recognize and obtain information about conspecifics and the infection and contamination threats they may pose.

Social recognition is the ability to distinguish and categorize con- Social learning in defined here simply as "learning that is influenced by observation of, or interaction with, another animal or its products" . [12] [13] [14] Social learning allows animals to save time and energy by circumventing costly trial-and-error learning and avoiding various costs and threats. Social learning allows individuals to exploit the previous experience of others and to respond to fluctuations in the immediate environment. Social learning entails deciding when and where to copy the behavior of others rather than learning asocially, as well as whose behavior and affective (emotional) states to copy. The degree to which social learning is used depends on the opportunities for social interaction, the extent to which behavior needs to be adjusted to changing social and environmental conditions, and how risky or costly it is to learn asocially.

Social cognition impacts on multiple aspects of social behavior and motivation (eg, social discrimination and recognition, familiarunfamiliar categorization, attention, decision making and social learning) that are relevant to the expression of disgust and pathogen/toxin avoidance. Social cognition involves not only successfully assessing other individuals and their behavior and condition (ie, actual or potential infection status and the risk of contamination they present), but also rapidly deciding whether, when, where and how to interact with them. 11, 15 For example mandrills and chimpanzees are able to gauge on the basis of social cues the infection status of their group members avoiding the parasite contaminated feces of neighbors and refraining from grooming infected conspecifics. 16, 17 Similarly, bonobos that are exposed to food contaminated with potentially infected conspecific feces modify their feeding decisions to minimize infection risk. 18 Here we briefly consider the social neuroscience of disgust. It has been suggested that the main olfactory system, which is sensitive to volatile odor cues, and not the VNO, is necessary for mate choice and sexual attraction. 39 However, it is possible that the aversive and avoidance responses to infected males involve both volatile and non-volatile odor constituents and most likely the accessory olfactory systems. There are data from mice indicating that the avoidance of a LPS treated conspecific requires normal functions of the VNO and possibly both volatile and non-volatile constituents. 45 Whether or not the disgust and avoidance responses to other infections similarly involve the VNO, as well as the relative roles of other olfactory components and receptors, remains to be clarified.

There is evidence that odor cues are also used to recognize and socially avoid infected same-and opposite-sex conspecifics in humans and non-human primates. 16, 17, 36, 46 In both humans and rodents stimulation of the immune system by systemic administration of LPS, results in a coordinated set of adaptive behavioral responses termed "sickness behavior". Sickness behavior constitutes an array of symptoms exhibited by animals during the course of infection, including fever, hypoactivity, reduced food and water intake and reduced social and exploratory behavior. 26 Rodents can detect and either avoid directly conspecific treated with LPS or detect and avoid the odors of individuals treated with LPS. 27, 47 In humans the axillary odors of men administered LPS were rated as less pleasant and healthy than either placebo treated individuals or prior to treatments. 36 Likewise the faces of individuals given LPS were rated as less desirable, with a further reduction with the presentation of LPS treated odor. 46 In this regard there is suggestive evidence that heightened olfactory sensitivity is associated with the augmented expression of disgust and enhanced perceptual vigilance. 2 These findings support parallels in odor based pathogen elicited disgust responses in humans and nonhuman animals.

Exposure to the odors of infected individuals also resulted in a decrease in nociceptive (pain) sensitivity and the induction of antinociception (analgesia). 4, [48] [49] [50] [51] [52] In female mice the nature of the analgesia varied according to the duration of exposure with prolonged exposures (15 minutes +) inducing a relatively long-lasting analgesia and brief exposures (30 seconds-1 minute) eliciting a shorter lasting analgesia followed by a protracted hypoalgesia. 49 Similarly, in humans brief exposure to disgusting infection associated images led to an initial analgesic responses followed by an increase in pain sensitivity. In a Y-maze odor preference test estrous female mice displayed an initial choice of and overall preference for the fresh urinary odors of uninfected (clean) males and an active discrimination against, and active avoidance of, and disgust responses to, the odors of males infected with an ectoparasite, the louse Polyplax serrata, (lousy males). Similar responses were seen when actual infested males were used. On day 1 the odor of the "lousy" was novel while on day 2 the odor of the male was either the same (familiar) or new (novel). Preference is defined as the duration of time the female spent in the stimulus arm of interest (lousy male) divided by the total time spent in the lousy + clean arms. The effects of the ecological (eg, predators, food availability, "noisy" backgrounds) and social context (eg, prior experience, degree of motivation, male availability, social networks and interactions, presence of other females and their choices on female mate and social partner choice) need to be considered.

Mate choice decisions do not necessarily occur in social isolation.

To reduce the risks and uncertainty associated with their own choice individuals pay attention to the mating choices of others. 60, 61 This non-independent process where individuals gain information about potential mates by either directly observing conspecifics or obtaining information from the cues associated with conspecifics' choices is termed "mate-choice copying" or mate copying. Mate choice copying has been mostly investigated with females in, which the preference toward a particular male as a mate by one female causes an increased preference for the same male in another female. 61 The dynamic social organization and interactions of rodents such as mice 58 provide opportunities for mate choice copying. In the wild females may be exposed to an index of another individual's mate choice rather than the actual mating. Male mice deposit urine which females investigate, 59 thus, leaving their own odors as source of information regarding their mate interest. Sexually naïve estrous female mice preferred the odors of a male that was associated with the fresh odors of an another estrous female, with this socially acquired odor preference translating into a choice for the specific male that was the odor source. 52 Similar odor-based mate choice copying has been reported from female rats and deer mice, as well male mice. 60, 61 Mate choice copying can override a females' initial choice and bias her preferences leading to the copying of a less desirable male. 67 There is evidence that in humans disgust is associated with a heightened sensory awareness, including that of odors and a greater salience of the negative sensory cues posed by out groups. 46 These threats may bias social preferences and interactions eliciting disgust and promote affiliation, interactions and cooperation with in-group individuals. Conversely, there are also suggestions that human disgust is attenuated by in-group relations rather than being augmented by out-group exposure, with the presence of familiar in-group members reducing odor elicited disgust. 70 This in-out-group discrimination has led to the suggestion of "assortative sociality" with perceived pathogen infection threat and elicitation of disgust favoring, social interactions between familiar individuals (in-group bias, ethnocentrism) with possibly also an increased sensitivity to and avoidance of unfamiliar individuals (outgroup avoidance, xenophobia). [64] [65] [66] [67] Responses to conspecifics can be affected by the social cues present at an initial appraisal, rather than by direct interaction with, and detailed knowledge of that individuals. In humans exposure to and, or priming with pathogen/parasite threat (eg, facial cues, odors) leads to more negative and avoidant responses to out-groups and heightened disgust. In parallel, the presence of out-groups or cues associated with them leads to heightened disgust and sensitivity to potential pathogen threat. 65 In humans pathogen threat directly affected women's perceptions of male attractiveness by increasing negative attitudes toward and decreasing interest and positive responses to unfamiliar and/or lower quality males. 71 Similarly, in mice the odors of an infected male rapidly decreased the subsequent responses to, and preferences for, unfamiliar males by estrous females. 25 The presence of an unfamiliar male also resulted in a heightened sensitivity to, and avoidance of, infected 
Test for Social Learning

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Unfamiliar -nonkin Unfamiliar -kin Familiar -kin FIGURE 2 Deer mice, Peromyscus maniculatus acquire defensive avoidance (disgust) responses (self-burying into cover provided by bedding) to biting flies (stable fly, Stomoxys calcitrans) through either individual or social learning. Through direct individual experience (acquisition dayexposed to intact flies) mice (demonstrators-DEM) learned to recognize biting flies and displayed rapid preparatory avoidances responses on the test days when they were exposed to altered flies with biting mouth parts removed. These anticipatory avoidance (disgust) responses were also acquired through social learning without any direct individual aversive experience with biting flies. Fly naïve observer (OBS) that witnessed a demonstrator being attacked by biting flies when exposed 1 to 3 later to altered flies displayed socially acquired self-burying avoidance (disgust) responses social learning of these avoidance responses to biting flies was modulated by kinship, familiarity, and dominance relations with observers that were either kin and, or familiar and subordinate showing better acquisition and faster avoidance responses. From Kavaliers et al 51 could not bite. These anticipatory avoidance, analgesic and corticosterone responses were also vicariously acquired through social learning without direct experience with biting flies. Fly naïve "observer" mice that witnessed other "demonstrator" mice being attacked and bitten by biting flies, but themselves were not bitten, displayed analgesic responses and elevated corticosterone. Twenty-four hours later observer mice that were exposed to altered flies without biting mouthparts, displayed socially acquired enhanced analgesic and selfburying avoidance responses. These responses were specific to biting flies and were not elicited by similarly sized house flies. As social learning can incorporate both the acquisition of affective states and 'emotional" states and the behavioral responses and choices of others the socially transmitted biting fly avoidance responses may be further interpreted as reflecting socially transmitted "empathy" to the pain and disgust responses of the demonstrator.
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Social learning often entails efficient social recognition with cues related to familiarity, relatedness and social status having been shown to enhance learning of fear, and food preferences. 48, 73, 74 The socially acquired disgust responses and empathy for disgust displayed by deer mice were facilitated by familiarity and, or kinship with the demonstrator. 48 As well subordinates showed enhanced learning from subordinates. Cues related to familiarity and relatedness have been similarly
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shown to modulate social transmission of fear (eg, electric shock) in rats and mice. 73, 75, 76 A similar effect of familiarity has been reported for social learning of distress in humans with cues from familiar members of in-groups eliciting greater responses. 72 In humans the transmission of fear and safety information is enhanced between individuals belonging to the same (in-group) and compared with different (out-group) racial groups as measured by conditioned autonomic responses. It should be noted that studies examining social modulation of fear have reported both social facilitation and social buffering. 77 Whether or not there is a similar social buffering of pathogen disgust remains to be clarified.
| DISGUST AND TOXIN DETECTION AND AVOIDANCE
All foraging animals face a dilemma. The items that provide them with nutrition may also expose them to pathogens and toxins. Behavioral The gaping response is similar to the orofacial topography of the retch response exhibited by the shrew. Suncus murinus, just prior to an emetic response and involves the same musculature.
| DISGUST AND TOXIN DETECTION AND AVOIDANCE
Rats as well as humans also display disgust responses upon exposure to a context that has been previously associated with a toxin or illness (anticipatory nausea; anticipatory disgust). [81] [82] [83] Rats can learn and remember associations, not only between distinctive tastes and experienced nausea, but also between distinctive contexts that were previously paired with nausea (eg, LiCl). They can subsequently retrieve these associations to show aversion-related disgust behaviors, such as gaping, upon re-exposure to the context in a drug-free state.
| DISGUST AND TOXIN DETECTION AND AVOIDANCE
Social factors also have a contextual role here leading to the expression of socially conditioned disgust responses and anticipatory nausea. Chemotherapy patients report that simply the sight of a nurse or oncologist alone is able to trigger feelings of disgust and nausea. 84 In fact, one oncologist reported that seeing a patient in a mall triggered vomiting and nausea in the patient. 85 Social factors also modulate anticipatory disgust in rodents. 78 Rats can associate a social partner with LiCl induced nausea displaying conditioned disgust (gaping) in the presence of the partner while in a drug-free state. They also displayed mixed approach-avoidance responses toward the social partner, suggestive of mixed signals of social buffering and facilitation of disgust, similar to that reported for fear.
77
There are also sex differences in the expression of nausea and conditioned disgust with females rats displaying significantly greater levels of anticipatory disgust than males. 81, 82 Similar sex differences in the propensity for disgust have been reported for humans 86 It is likely that parasite and pathogen/toxin behavioral avoidance responses, the expression of disgust and anticipatory disgust occurs in a sexually dimorphic manner over a range of situations.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
The expression of disgust and the recognition and avoidance of pathogen/parasite/toxin threat involves a variety of neurobiological regulatory mechanisms that allow individuals to rapidly evaluate, integrate and respond to social information derived from parasite and pathogen/toxin threats into adaptive disgust associated recognition and avoidance behaviors. 4, 11 These neuromodulatory mechanisms include:
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
various evolutionarily conserved neurotransmitters, in particular dopamine and serotonin in the "mesolimbic reward system" and "social In a Y-maze odor preference test oxytocin (OT) wild type OTWT females showed a marked initial choice for the odors of uninfected males and avoidance of the fresh urinary odors of males infected with intestinal nematode Heligmosomoides polgyrus, whereas oxytocin knockout (OTKO) females showed no consistent initial choice, preference or disgust responses. On day 1 the odor of the infected male was novel while on day 2 the odor of the male was either the same (familiar) or new (novel). Similar responses were seen when actual infested males were used.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
Modified from Kavaliers et al 48 likelihood that the effects of OT are just fear related. In addition, these responses were not associated with any impairment in the ability to distinguish social odors (eg, castrated vs intact male).
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
Chemosignals are detected by the VNO and main olfactory systems and that information is conveyed to the amygdala and other sites in the central social network. OT and OT receptors in the medial amygdala are critical for social recognition [96] [97] [98] and are a likely mediator of the altered behavioral responses to infected males. In addition,
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
OT in the pyriform cortex and anterior olfactory cortex is involved in the modulation of odor mediated social recognition and the encoding of the saliency of social odors. 90 This is consistent with the findings that exposure to the odors of LPS treated human subjects led to an increased activation of the orbitofrontal cortex, piriform cortex, amygdala and insular cortex. 46 OT has been shown to affect olfactory processing in a social context and influence social recognition. 94 OT may convey social salience in different sensory modalities leading to a more broadly based pathogen/parasite detection and expression of disgust and avoidance behaviors.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
OT is also implicated in the mediation of the in-group bias and outgroup avoidance associated with pathogen threat. Prior treatment with an OT antagonist attenuated the aversive and avoidance responses to unfamiliar male mice displayed by female mice following exposure to infected individuals (in preparation). This is consistent with the report that exposure to a stressor elicits OT mediated social avoidance in female deer mice. 95 In humans, OT and to a lesser extent, AVP also have been implicated in the mediation of social cues promoting intergroup discrimination. 65, 92 Intranasal OT augments positive responses to members of in-groups and negative responses to out-group members and promotes intergroup discrimination. 65 OT also amplifies intergroup recognition and discrimination leading to differential treatment of inand out-group members, accompanied by enhanced vigilance/anxiety toward out-groups. Through its modulation of corticoamygdala circuits OT also permits the expression of disgust and the display of behavioral avoidance responses to out-group threat. 91 A basic role of oxytocin may be to increase vigilance, defensive aggression, coupled with expression of disgust associated behaviors, to protect oneself and ingroup members against out-group threat.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
OT is also involved in the mediation of social learning and the expression of mate choice copying. 52, 61 OTKO female mice and females treated with an OTR antagonist were impaired in their use of social information and did not copy the odor based mate choices, including that of parasitized males, of other females. This is consistent with the involvement OT in increasing the salience of, and attention and approach to, positive social stimuli in humans. 92 OT is also proposed to be involved in the mediation of empathy in humans by modulating amygdala activity and amygdala-cortical connectivity. 99 It is conceivable that during mate choice copying female mice may be displaying empathy with, and attributing a greater OT mediated positive salience to, the mate interests of other females, especially those that are familiar and kin.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
OT is also involved in the social transmission of fear and empathy for fear in mice in part through effects on the anterior cingulate cortex (ACC). 73 Recent evidence suggests that ACC neurons represent socially derived aversive cue value and that this information is transmitted to the basolateral amygdala where an association between the cues and the affective responses of the demonstrator are found. 100 It is conceivable that OT may be similarly involved in the mediation of the social transmission of pathogen disgust and empathy for disgust.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
The bi-directional effects of OT on approach/avoidance according to the social salience of the sensory inputs could facilitate both pathogen avoidance and mate choice copying of infected individuals.
| NEUROBIOLOGY OF DISGUST AND PATHOGEN/TOXIN AVOIDANCE
Oxytocin has also been linked to the expression of toxin elicited disgust. OT is involved in the modulation and expression of socially mediated conditioned disgust, with treatment with an OT antagonist attenuating the expression of anticipatory nausea (disgust) in male rats as well as the bi-directional approach/avoidance behaviors. 78 This is consistent with the suggestion that OT is associated with the expression of human disgust, including that which is socially mediated. Although the majority of studies have focused on OT there is evidence for the involvement of AVP in the mediation of social recognition, although likely more so in males than females. 105 In general the effects of OT are linked to estrogenic mechanisms while those of AVP are more testosterone-dependent. 19 The specific roles of AVP in social cognition and the expression of disgust require further investigation.
| Estrogens, disgust and pathogen/toxin avoidance
Gonadal steroid hormones have an important role in the regulation of social behaviors with estrogenic systems, in particular, being involved in the regulation of the expression and utilization of social information. 20, 87, 106, 107 This ranges from the detection and processing of olfactory information to odor production, social recognition, social learning to the expression of complex social behaviors including sexual behavior. These effects are mediated through a number of estrogen receptors (ERs). The most studied ERs are ERα, ERβ and the G protein coupled ER 1 (GPER1) which can mediate both rapid non-genomic and the more delayed and lasting classical genomic effects. 87 ERα and GPER1 have been shown to rapidly facilitate social recognition and social learning with the effects of ERβ being less well defined. 87, 107 Estrogenic mechanism and ERα and ERβ have been implicated in the expression of disgust and pathogen/toxin avoidance. Female ERα and ERβ gene deleted mice (ERαKO and ERβKO mice) were impaired both in their ability to discriminate between the odors of infected and uninfected individuals and to distinguish between familiar and unfamiliar individuals. 11, 20 The ERαKO and ERβKO mice displayed minimal aversive disgust associated responses to the odors of infected individuals. There were, however, no significant differences in either olfactory sensitivity or sexual interest of the estrous KOs and wild types.
| Estrogens, disgust and pathogen/toxin avoidance
There are sex differences in the formation of conditioned disgust (gaping behavior) in rats with females showing markedly greater responses than males. In females estrous phase affects the expression of conditioned disgust with the greatest levels seen in proestrous when elevated levels of estrogens and progesterone are present. 81, 82 These effects may be related to estrogen mediated hippocampal dependent enhancement of memory formation (eg, 87, 108 ) that is required for the expression of for anticipatory nausea and anticipatory conditioned disgust. As well the sexually dimorphic effects may be associated with a more specific involvement of estrogenic mechanisms in the elicitation of disgust as suggested for the detection and avoidance of infected individuals and the elicitation of pathogen disgust. Results of prior studies have shown that estradiol can produce conditioned taste avoidance when paired with a novel sucrose solution, as well as conditioned aversion consisting of disgust responses to the sucrose taste. 109 Estradiol has also been shown to enhance the acquisition of LiCl-induced taste aversion in castrated male rats, 110 possibly due to estradiol's illness inducing properties. In addition, the formation of conditioned taste aversion and reduction of food intake seen after administration of agonists for ERα, ERβ and GPER-1 is likely associated with the nausea and potentially disgust related responses elicited by estrogens,. 111, 112 These actions may also be related to ERs association with OT which is involved in the elicitation of anticipatory disgust. 78 Oxytocin has been implicated in the expression of the effects of ERs on social recognition and the display of the disgust and avoidance responses to pathogen threat. Both ERβ and GPER are considered to be involved in the regulation of the synthesis and release of OT at the level of the hypothalamus. 87 All three ER receptors are expressed in the medial amygdala where they enhance social recognition and likely are associated with the functioning of the OTR. 11, 20, 96 Estrogens in the paraventricular nucleus rapidly facilitate social recognition, an effect that was blocked by OTR antagonists in the amygdala (, 113 in preparation), while estrogens in medial preoptic area of female mice have been associated with the rewarding effects of male odors facilitating dopamine release at the level of the ventral tegmental area. 107 It is possible that such interactive mechanism may be associated with the expression of pathogen and toxin disgust associated with ERs.
| Estrogens, disgust and pathogen/toxin avoidance
The roles of progesterone which is selectively associated with the indifference shown by diestrous female mice to MUP associated male odors, need to be examined. 114 In particular, how this relates to progesterone's proposed enhancement of disease and toxin avoidance in human females 115 needs to be examined. As well, the potential interaction with OT and other neuromodulators needs consideration.
| CONCLUSIONS AND FUTURE DIRECTIONS
The These findings have direct bearing on issues associated with the expression of disgust and the landscape of disgust found in nature.
| CONCLUSIONS AND FUTURE DIRECTIONS
Avoidance of parasitized and diseased conspecifics as well as toxins and contaminants is universal. 2, 4 This is particularly relevant to the increasing threat of new and emerging diseases and contaminants.
| CONCLUSIONS AND FUTURE DIRECTIONS
Accumulating evidence from humans is also pointing to the important roles that disgust and its underlying pathogen/toxin elicitors has in shaping our political and societal mores (eg, ethnocentrism, xenopho- There are also sex differences in the display of disgust and pathogen/toxin recognition and avoidance. Understanding how sex differences in social cognition and their neuroendocrine substrates contribute to the expression of disgust pathogen/toxin recognition and avoidance is critical. Understanding the mechanisms underlying the display of disgust and how pathogen/toxin recognition and avoidance are achieved is important for our understanding of human and non-human social behavior and community dynamics.
ACKNOWLEDGMENTS
The studies described here were supported by Natural Sciences and 

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