The ability to appropriately adjust behavior in a social context is performed daily and is impacted in several psychiatric disorders (Baron-Cohen et al., 1985; Blair, 2003; Cook and Black, 2012; Gaigg, 2012; Hamilton, 2013; Matthys et al., 2013; Neuhaus et al., 2010; Rizzolatti and Fabbri-Destro, 2008; Scott-Van Zeeland et al., 2010; Taylor and DeQuinzio, 2012). However, it is unclear how neurobiological substrates integrate harm of others into our decisions because detailed work in animals at the single-unit and neurotransmitter level has not yet occurred. A growing number of high-profile reports have demonstrated that rodent models can be used to perform such experiments (Atsak et al., 2011; Ben-Ami Bartal et al., 2011; Ben-Ami Bartal et al., 2014; Burkett et al., 2016; Church, 1959; Guzmán et al., 2009; Hernandez-Lallement et al., 2018; Hernandez-Lallement et al., 2018; Hernandez-Lallement et al., 2017; Jeon et al., 2010; Jones et al., 2014; Kashtelyan et al., 2014; Kim et al., 2010; Langford et al., 2006; Masserman et al., 1964; Meyza et al., 2017; Mogil, 2015; Panksepp, 2011; Panksepp and Lahvis, 2011; Sato et al., 2015; Schaich Borg et al., 2017). For example, rats have been described as ‘empathetic’ and ‘prosocial’ because they freeze when they see others freeze in response to threat and will rescue conspecifics from distress when given the opportunity (Atsak et al., 2011; Ben-Ami Bartal et al., 2011; Ben-Ami Bartal et al., 2014; Meyza et al., 2017). These prosocial behaviors are particularly strong when rats are cage mates and in situations in which there are no explicit negative consequences to the rat performing the prosocial act.

Although we often perform prosocial actions that benefit others and suppress actions that might cause harm to others, there are other circumstances where this does not occur. This is especially true when our own sacrifice is too great or when the benefactor is not a friend, family member, or somebody believed to not reciprocate. How we respond to the distress of others is also modified by potential consequences for oneself. That is, we might feel distress when aversive events happen to somebody else, but in other contexts in which we are also at risk, we might be relieved that our own self-interests were not affected. Here, we show that rats can be more interested in their own physical state (subjective value) as opposed to another’s (objective value), which we will refer to as ‘self-interested’. Further, we demonstrate that subsecond dopamine (DA) release in nucleus accumbens core (NAc) accompanies this regard for one’s own interest, reflecting the subjective value placed on appetitive and aversive events as opposed to the objective value of the event itself.

The DA system is unique in that it is the only neurotransmitter system that genuinely signals all aspects of reward prediction error encoding (Bayer and Glimcher, 2005; Bromberg-Martin et al., 2010; Day et al., 2007; Gan et al., 2010; Hart et al., 2015; Hart et al., 2015; Roesch et al., 2010; Schultz, 2010; Schultz et al., 2015; Schultz et al., 1997). By using a variety of technical approaches across species, studies have shown that DA neurons in the ventral tegmental area (VTA) and subsequent DA release into the NAc increases and decreases in response to events that are better or worse than expected, respectively. In the appetitive domain, cues that predict reward or the uncertain delivery of reward increase DA release, and cues that predict less favorable reward and omission of expected reward decrease DA release. In aversive contexts, cues predictive of unavoidable aversive events (e.g., quinine, air puff, shock) or delivery of those aversive outcomes themselves robustly reduce DA release, whereas unexpected omission of aversive events or the cues that predict avoidable shock reliably elicit phasic DA release (McCutcheon et al., 2012; Oleson et al., 2012; Roitman et al., 2008; Wenzel et al., 2018).

We therefore asked how DA signals are modulated by appetitive and aversive events that occur not to the animal from which recordings were obtained, but from a conspecific located nearby. To achieve this, we recorded accumbal subsecond DA release using fast-scan cyclic voltammetry (FSCV) in two different social paradigms: one that used Pavlovian cues to predict unavoidable shock to the recording rat or to a nearby conspecific; and another that had an instrumental component (lever press), which allowed the recording rat to refrain from the pursuit of reward when there were known harmful consequences (i.e., footshock) for itself or the conspecific.

In both studies, we found signs that rats were ‘empathetic’ and/or ‘pro-social’ as described above. Rats refrained from pressing for reward to spare the conspecific from shock and DA release mirrored trials when the rat we recorded from made the same decision for itself. Further, we show that when the recording rat was in the presence of the conspecific it displayed less fear and reduced DA inhibition to cues that predicted unavoidable shock. However, our results also show that rats are often not overly empathetic or prosocial; their behavior and DA signals were modulated by potential reward and shock that occurred directly to them as opposed to the conspecific, reflecting subjective rather than objective value. Specifically, we found that DA was released when the conspecific was shocked instead of the rat being recorded from and that DA signals reflecting the value of shock avoidance were weaker when the conspecific was spared.

This study is significant given the absence of work examining modulation of neural signals in social tasks where conspecific distress impacts behavior and decision making. Importantly, patients with psychopathic traits and autism have difficulties recognizing the mental states of others and appropriately altering behavior in social contexts (Baron-Cohen et al., 1985; Blair, 2003; Buckholtz et al., 2010; Cook and Black, 2012; Gaigg, 2012; Hamilton, 2013; Matthys et al., 2013; Neuhaus et al., 2010; Rizzolatti and Fabbri-Destro, 2008; Scott-Van Zeeland et al., 2010; Taylor and DeQuinzio, 2012). These disorders are difficult to treat and currently lack effective pharmacological interventions, reflecting the lack of knowledge pertaining to our understanding of the underlying neurobiology of how social cues may alter behavior.

Although empathy and prosocial behavior might be considered a trait unique to primates, a number of recent studies suggest that rats can display similar behaviors (Atsak et al., 2011; Ben-Ami Bartal et al., 2011; Ben-Ami Bartal et al., 2014; Burkett et al., 2016; Church, 1959; de Lecea et al., 2006; Guzmán et al., 2009; Hernandez-Lallement et al., 2018; Hernandez-Lallement et al., 2016; Hernandez-Lallement et al., 2017; Jeon et al., 2010; Jones et al., 2014; Kashtelyan et al., 2014; Kim et al., 2010; Langford et al., 2006; Masserman et al., 1964; Mogil, 2015; Panksepp, 2011; Panksepp and Lahvis, 2011; Sato et al., 2015). For example, rats will choose mutual reward in a prosocial task, freeze when they see another rat freeze (interpreted as ‘empathy’) and exhibit ‘prosocial’ rescue behavior of a conspecific in distress. Most notable was a recent set of high profile papers (Science; eLife) demonstrating that rats will rescue a conspecific that is confined in a restrainer, even when faced with a choice between freeing the trapped rat and obtaining food reward (Ben-Ami Bartal et al., 2011; Ben-Ami Bartal et al., 2014). Although many of these studies are intriguing, they have met criticism; effects are often small, rats only freeze when they have experienced shock themselves, and rats do not free trapped conspecifics under all circumstances (Schwartz et al., 2017; Silberberg et al., 2014). Further, many of these effects are dependent on rats being cage mates or of the same strain, suggesting that ‘prosocial’ rescue behavior might reflect some sort of reproductive benefit.

It is well-known that activity of DA neurons and DA release in NAc increases and decreases to events that are better and worse than expected, respectively (Bayer and Glimcher, 2005; Bromberg-Martin et al., 2010; Day et al., 2007; Gan et al., 2010; Hart et al., 2015; Hart et al., 2014; McCutcheon et al., 2012; Roesch et al., 2010; Schultz, 2010; Schultz et al., 2015; Schultz et al., 1997). This is true across species, techniques and tasks. Indeed, in our task, reward delivery and cues that predicted reward delivery, increased DA release when they were directed to the recording rat. Similarly, cues that predicted unavoidable shock inhibited DA release when it was the recording rat that was to be shocked. Importantly, cues and outcomes directed to the conspecific did not produce the same pattern of results, suggesting that – if DA signals genuinely reflect value of predictive cues – cues that predicted conspecific reward and shock were not considered to be appetitive and aversive, respectively. Moreover, footshocks directed to the conspecific actually increased DA release, suggesting that rats may have been using cues from conspecific (e.g., vocalizations, odors, visual, etc.) to determine that the shock had been delivered to the conspecific, signaling the value of personal safety or relief. This interpretation is supported by the freezing and approach behavior at the time of the shock. The rat that we recorded from approached the other rat during the outcome, but did not freeze. This suggests that the recording rat was engaged with the conspecific possibly to determine what will occur during the trial, but was not overly fearful during that period (i.e., the period when DA increases during conspecific shock). If rats were more strongly displaying empathy or the objective value of the conspecific shock, DA release would be inhibited to a stronger degree and rats would freeze more to the conspecific being shocked compared to when a shock is applied to the empty box. This is a very interesting aspect of the data and can only be obtained when trials are anti-correlated. Of note, in previous ‘empathy’ studies there were no real consequences to the animal when a negative event occurred to the conspecific. Here, it appears that the ‘relief’ or ‘safety’ aspect stemming from the situation, through negative reinforcement processes, outweighed any signals that reflect the evaluation of the nature of the outcome from the perspective of the conspecific. We do not believe that DA signals ‘relief’ or ‘empathy’ per se, but reflects prediction error correlates that are informed by social contexts. In this case, since the trial types are anti-correlated, DA increases because the rat being recorded from did not get shocked, eliciting a positive prediction error. Nevertheless, our data does not unambiguously demonstrate that the response is due to the rat's own safety and it remains unclear whether we can completely exclude the possibility that this response is due to the outcome presented to the conspecific. Disambiguating this point requires additional control experiments that would require isolating DA signals during conspecific alone when there are no self-shock trials. This might help dissociate signals related to relief/safety from those that represent the conspecific’s outcome; however, it is known that rats will not display empathy while watching another rat get shocked unless they too have been shocked. Thus, rats may not internalize ‘conspecific outcome’ until they have experienced the negative outcome themselves making this a difficult issue to reconcile.

Overall, these results suggest that DA release signals the subjective value placed on events that occur to the conspecific similar to what has been described previously in the appetitive domain (Dal Monte et al., 2018; Kashtelyan et al., 2014; Noritake et al., 2018). Remarkably, we also found that the presence of the other rat altered the subjective value placed on cues that predicted self-shock by reducing fear and the associated suppression of the DA signal during the Pavlovian paradigm. On these trials the rat approached the conspecific, perhaps reflecting ‘consolation’ seeking behavior similar to what has been described in prairie voles (Burkett et al., 2016). The lack of suppression of DA release during this period suggests that the recording rat found the shock cue to be subjectively less aversive in the presence of the conspecific. Indeed, rats entered the food cup and froze less often on together-shock-self trials. Importantly, these results differ from what has been described in prairie voles; that is, a prairie vole that is not in distress will approach another vole that is in distress. In our task, approach was mostly one-sided in that the recording rat approached the conspecific far less on shock-other trials.

In the context of the instrumental task rats pressed significantly less and were slower to press on conspecific-shock trials, demonstrating empathetic and prosocial behaviors consistent with previous reports (Atsak et al., 2011; Ben-Ami Bartal et al., 2011; Ben-Ami Bartal et al., 2014; Burkett et al., 2016; Meyza et al., 2017). Remarkably, DA release during decisions to give up reward and spare the conspecific from shock mirrored DA release when the rat avoided shock for itself, suggesting that DA release during conspecific shock trials reflected the value of saving the conspecific similar to when it signals the value of saving oneself and that the same signal that encourages avoiding shock for oneself is present when avoiding shock for a conspecific. However, lever pressing increased and DA release decreased during conspecific-shock compared to self-shock, which indicates that rats were more interested in sparing themselves from harm rather than sparing the conspecific. This suggests that the DA signal is modulated by the degree of ‘empathy’ exhibited by rats in the context of this task. Importantly, as above, we do not think that DA is signaling empathy per se, but represents modulation of prediction errors in this task by empathy, reflecting the subjective value placed on avoiding conspecific shock.

The behavior described here demonstrates that rats do not always demonstrate ‘empathetic’ and ‘prosocial’ behavior as described previously or as expected in humans. This may be overly apparent in our tasks where there is a real consequence to performing the prosocial act (i.e., no rewards on that trial), a looming threat that an upcoming trial might result in personal shock, and no alternative reward (i.e., social contact; explore the restrainer). Although rats might not exhibit human-like empathetic or prosocial behavior in our tasks, to be fair to rat-kind, it is unclear how humans would act in similar tasks when no one is watching. Altogether, our results suggest that there might be something unique about previously published work that does not completely generalize across behavioral contexts – that the unique structure of previous experiments promotes stronger empathy and pro-social behavior, especially when there is not much cost to the actor. Importantly, across studies (ours and others) we don’t think that these differences reflect problems with task design (ours or others), but that each task structure promotes different levels of ‘pro-social’ and ‘empathetic’ behavior along a continuum, providing insights into social behavior, and how the brain governs behavior and interprets outcomes in social contexts.

It is possible that prosocial and empathetic behavior may have been more prominent in our paradigms if rats were cage mates; however, previous work has shown that rats will help ‘trapped strangers’ by releasing them from the restrainer, just as they do for cage mates so long as they were of the same strain (Ben-Ami Bartal et al., 2014). In our study, rat pairs were of the same strain, and were well acquainted in that they had been shipped together in the same box, were paired together in the recording boxes for the entirety of the experiment, and rat pairs resided next to each other in transparent cages in the animal colony. However, we cannot rule out that physical contact may be necessary to promote stronger empathic and prosocial behavior.

It is important to note that our goal was not to uncover the exact correlates of social behavior for we do not believe the sole purpose of this brain circuit is to make social decisions, rather, the purpose of these studies were to understand how social contexts impact decision making and reinforcement circuits, with the hope that we will uncover the cogs in the greater machinery that contribute to complex behaviors (e.g., empathy, prosocial, egocentric or self-interested) in different social contexts. For the first time, we show that DA release is modulated by social context in at least three ways. First, reductions in DA release during cues that predict foot shock were weaker in the presence of the conspecific, likely due to comfort or distraction of being in the presence of another rat as evidenced by seeking social contact prior to and during foot shock delivery when together, but not alone. Second, DA release during shock trials increased when shock was administered to the conspecific, demonstrating that DA release was modulated by conspecific cues that indicated that the foot shock had occurred on the other side of the box. This result may reflect an external signal that foot shock would not occur to the recording rat. Third, during the instrumental task, cues that predict avoidable foot shock for the conspecific elicited a similar, but weaker DA release compared to cues that predicted avoidable foot shock for oneself. Overall, we conclude that DA release is modulated by social context in that rats use social cues to optimize predictions about their own self-interest, even at the expense of a conspecific, and that correlates related to avoidance are present, albeit weaker, when consequences are directed to another rat as opposed to oneself.

Data has been uploaded to Digital Repository of the University of Maryland (https://dx.doi.org/10.13016/M2804XP75).

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Author details

1. Nina T Lichtenberg

   Department of Psychology, University of Maryland, College Park, United States

   Contribution

   Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing

   Contributed equally with

   Brian Lee

   Competing interests

   No competing interests declared

2. Brian Lee

   Department of Psychology, University of Maryland, College Park, United States

   Contribution

   Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing

   Contributed equally with

   Nina T Lichtenberg

   Competing interests

   No competing interests declared

3. Vadim Kashtelyan

   Department of Psychology, University of Maryland, College Park, United States

   Contribution

   Conceptualization, Data curation, Formal analysis, Supervision, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing

   Competing interests

   No competing interests declared

4. Bharadwaja S Chappa

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

5. Henok T Girma

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

6. Elizabeth A Green

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

7. Shir Kantor

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

8. Dave A Lagowala

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

9. Matthew A Myers

   Gemstone Honors Program, University of Maryland, College Park, United States

   Contribution

   Data curation, Formal analysis, Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

10. Danielle Potemri

    Gemstone Honors Program, University of Maryland, College Park, United States

    Contribution

    Data curation, Formal analysis, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

11. Meredith G Pecukonis

    Gemstone Honors Program, University of Maryland, College Park, United States

    Contribution

    Data curation, Formal analysis, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

12. Robel T Tesfay

    Gemstone Honors Program, University of Maryland, College Park, United States

    Contribution

    Data curation, Formal analysis, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

13. Michael S Walters

    Gemstone Honors Program, University of Maryland, College Park, United States

    Contribution

    Data curation, Formal analysis, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

14. Adam C Zhao

    Department of Psychology, University of Maryland, College Park, United States

    Contribution

    Data curation, Formal analysis, Methodology, Writing—review and editing

    Competing interests

    No competing interests declared

15. R James R Blair

    Center for Neurobehavioral Research, Boys Town National Research Hospital, Boys Town, United States

    Contribution

    Conceptualization, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

16. Joseph F Cheer

    1. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, United States
    2. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, United States
    3. Program in Neuroscience, University of Maryland School of Medicine, Baltimore, United States

    Contribution

    Conceptualization, Investigation, Writing—review and editing

    Competing interests

    No competing interests declared

17. Matthew R Roesch

    1. Department of Psychology, University of Maryland, College Park, United States
    2. Gemstone Honors Program, University of Maryland, College Park, United States
    3. Program in Neuroscience and Cognitive Science, University of Maryland, College Park, United States

    Contribution

    Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Investigation, Visualization, Methodology, Writing—original draft, Project administration, Writing—review and editing

    For correspondence

    mroesch@umd.edu

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-2854-6593

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