Of Course They Do!
Our children from their earliest years must take part in all the more lawful forms of play, for if they are not surrounded with such an atmosphere they can never grow up to be well conducted and virtuous citizens.
—Plato, The Republic
LET US START THIS DISCUSSION of personality of our “fellow travelers” with a seemingly outrageous claim: We have learned more about the fundamental neural nature of human emotions (e.g., the subcortical neural circuits and neurochemistries) by studying the brains of laboratory rats than those of human beings. Indeed, the study of their brain emotional systems has proved to be a very effective strategy for the development of new and highly effective antidepressants, one of them from the study of the happy sounds (50 kHz chirps) they make when they play (Burgdorf, Panksepp, & Moskal, 2011; Panksepp, 2015, 2016). And when we breed males and females that show abundant “rat laughter,” we have developed lines of animals that can more easily sustain positive moods and are resistant to depression. On the other hand, when we breed rats that are sourpusses (i.e., laugh very little when they are tickled), they more readily succumb to depression when stressed (Burgdorf et al., 2011; Burgdorf, Colechio, Stanton, & Panksepp, 2017; Burgdorf & Panksepp, 2006; Panksepp, Burgdorf, & Gordon, 2001).
To raise a controversial point (on which our group has more data than anyone else), we may be learning more about the subcortical fundamentals of our own laughter/joy circuits (and the neural constitution of positive affect) by studying rat brains than those of human beings—we seem to share the same fundamental subcortical circuits for such feelings (Roccaro-Waldmeyer, Babalian, Müller, & Celio, 2016). Of course, all this does not mean rats tell jokes to each other, but they surely have abundant playful fun.
Indeed, most young laboratory rats are as playful as human children, and indeed, we have learned more about the play circuitry of mammalian brains (but not their jokes) by studying rat brains than human ones. And it looks like our human laughter circuitry arises from the same ancient subcortical brain systems as rats (Burgdorf et al., 2007; Panksepp, 2000b, 2007c). Of course, for most who have not done such studies, these claims may seem outrageous.
BACKGROUND REFLECTIONS ON LABORATORY RATS (DOMESTICATED RATTUS NORVEGICUS)
Rats are mammals, but could these little beady-eyed rodents have complex interesting personalities like dogs, chimpanzees, and humans, or is that a fishy proposition (which we will touch on in the next chapter)? That surely depends, in part, on what kind of rats we are talking about. The laboratory rat, which is used extensively in medical and behavioral research, is a highly domesticated animal that has been bred for generations to accept human handling and companionship. While precise numbers are not available, the Federal Research Division of the Library of Congress found as many as 1 million rats were used for research in 2000. Data from the United Kingdom suggested that 414,335 rats were used in 2005 just in that country. These lab animals are purposely bred to be docile and in the laboratory are typically housed individually in separate cages, which has certainly altered their temperaments, perhaps making them almost immune to separation distress (for discussion, see Panksepp, 2003). The lab rat’s wild relative, Rattus norvegicus, the common brown rat, has a major public relations problem but has so far evaded all of the human race’s attempts to exterminate it. This wild relative undoubtedly has more variability in its temperament, but you may be surprised at how much personality even lowly lab rats can display when given the chance.
One of the main advantages of laboratory rats (and mice) is their combination of docility, fecundity, rapid maturation, and all the organs and all the brain systems that humans have (but in miniature, of course). Because many writers, including Darwin, have noted that being able to selectively breed for a behavior characteristic is strong evidence of its genetic basis, rodents’ capacity for rapid multiplication has often made them subjects of a great diversity of selective breeding efforts. Much of what is known about rat personality comes from breeding for extreme emotional traits, and several such focused projects working with single emotions are reviewed in this chapter, in contrast to the types of projects seen with primates and dogs that attempt to assess a broad array of the animals’ personalities.
The abundance of behavioral emotional research in laboratory rats (and mice) has yielded clear evidence for the heritability of more affective temperamental traits in warm-blooded mammals than have ever been demonstrated in cold-blooded vertebrates such as fish (see Chapter 10). The inheritance of the evolutionarily older RAGE/Anger and FEAR brain systems has been demonstrated multiple times in so-called gene knockout strains of mice (which have specific genes selectively inactivated) where elevations of both of these traits are evident (Crawley, 2007). Here, we focus on research using lab rats, which has confirmed the evolutionarily more ancient biologically endowed emotions of SEEKING, RAGE/Anger, and FEAR, as well as the socially oriented emotional systems of LUST, CARE/Maternal nurturing, and PLAYfulness, but perhaps less so for PANIC/Sadness (separation distress, which may have been selected against during domestication, because it was desirable for behavioral research to have animals living alone, one to a small cage; Panksepp, 2003). Most of these emotional systems are easily studied in laboratory rodents, and accordingly, we would argue they have been evolutionarily layered onto rodent personalities, which may serve as neuroscientific models for the study of the fundamentals of most primary emotional feelings. Such work may enable in-depth studies of the neural foundations of mammalian temperaments, which we believe further support a biological foundation for the primary affective traits that account for a great deal of human personality differences.
SELECTIVE BREEDING AND THE FEAR SYSTEM
Selective breeding is nothing new in the biopsychological world. There were several early research programs of behavioral selection for temperamental fear in rodents. Calvin Hall, who spent most of his career at Western Reserve University, devised what he called a strange (i.e., novel), open-field situation, which provoked rat emotionality or excitability, or what we would label fear (Hall, 1934a). He used his new open-field test to select for and breed high and low fear strains of rats (Hall, 1941). Interestingly, Hall received his Ph.D. at the University of California, Berkeley working with Edward Tolman and Robert Tryon. At that time, Tryon was in the process of selectively breeding his maze “bright” and “dull” strains of rats to demonstrate the influence of genetics on learning processes in an era dominated by behaviorist learning theory, which emphasized that environmental rather than genetic differences controlled individual behavior differences. (Of course genetics was in its “fetal,” preinfancy in those days.) Thus, it is not surprising that Hall used his open-field device so successfully to selectively breed high and low fear strains.
He placed rats in a brightly lit, eight-foot-diameter, round box that rats found stressful, because it was a strange, bright place with nowhere for a normally nocturnal prey animal to hide. He mated the male and female rats that showed the most emotional defecation and urination in the open-field test, to create a high fear line of rats, and the male and female rats showing the lowest stress-induced eliminative behaviors, yielding a low fear line (Hall, 1934b). Following this procedure for each subsequent generation, Hall found gradually increasing fear differences between the two strains during eight generations of selective breeding.
A more recent program used the elevated plus-maze to selectively breed rats for high anxiety-related behavior (HAB) and low anxiety behavior (LAB; Liebsch, Montkowski, Holsboer, & Landgraf, 1998). The elevated plus-maze was designed to elicit a rat’s innate fears of open and elevated spaces. It is usually elevated about two feet from the floor and has two four-inch wide crossing arms constructed in the shape of a plus sign. One of the arms is completely open with no sides. The other arm has walls on all sides except in the center where the two arms cross, that is, a center area allowing entry into the walled or open parts of the maze. The enclosed arm is usually dark and the open arm brightly lit, which also addresses the nocturnal rat’s natural preference for dark places. Typically, all rats explore the parts of the maze with walls with the more fearful animals avoiding the open arm with no walls.
In the Liebsch et al. (1998) breeding program, rats with less activity in the open arms (fewer entries and less time spent in the fear-provoking arms) were selected and bred to create the HAB line, and those with more activity in the open arms became the parents in the LAB line. Other tests showed that HAB animals spent less time in the center of an open field, thus validating that the HAB line experienced more fear than LAB animals in an open-field test. HAB animals also struggled less when first exposed to a forced swim test, which further suggested a possible depressive tendency in the HAB line (Liebsch et al., 1998).
Cross-fostering on these lines failed to reveal any maternal developmental influences (Wigger, Loerscher, Weissenbacher, Holsboer, & Landgraf, 2001), and crossbred F1 and F2 hybrids were intermediate to the pure HAB and LAB lines on all plus-maze fear measures, both findings consistent with genetic inheritance. We would note that human families sometimes naturally produce such crossbreeding results. That is, sometimes a person with a high fear phenotype marries a person with a low fear phenotype, and on average the couple produces children with intermediate fear sensitivities, although with the complex FEAR system, some children may track closer to the high or low fear sensitivity parent.
Interestingly, at ten days of age HAB rat pups also emitted more 40-kHz vocalizations than did LAB pups (Wigger et al., 2001). It would be relevant to determine whether these HAB rats also emitted more adult 22-kHz alarm calls, which would clearly indicate more negative affect as adults (more on rat vocalization later). Further confirming evidence included higher levels of stress indicators such as ACTH, corticosterone, and prolactin in HAB versus LAB male rats, especially when exposed to the plus-maze with no access to the enclosed arm.
Treatment for seven weeks with the SSRI antidepressant drug paroxetine (Paxil) also brought the active struggle time of the HAB rats in the forced swim test up to the level of the LAB rats (Landgraf & Wigger, 2002), which again suggested a possible depressive component in the HAB line. However, more specifically targeting fear levels, injections of the anti-anxiety drug diazepam (marketed as Valium), a highly effective antianxiety medication in the benzodiazepine group, increased the percentage of time spent in the plus-maze open arms twenty-fold in HAB rats (with a less dramatic increase of 2.5-fold in LAB animals) and increased the speed to enter the open arm sevenfold in HAB rats (only twofold in LAB line). While fear in the HAB line was dramatically relieved by diazepam, even after many generations of selection the LAB line apparently also retained the capacity to experience fear, because they also responded less fearfully after the diazepam treatment. The fact that even the LAB line continued to experience fear suggests that a potent deeply engrained FEAR system exists in the brain. Indeed, Panksepp (1971) and others have demonstrated that a powerful flight response can be evoked by stimulating specific regions in the hypothalamus, and animals given a chance will turn off the brain stimulation that activates such FEAR responses. That after the diazepam the LAB rats still experienced FEAR/Anxiety suggests that the FEAR system is likely to remain an adaptive tool for living in all mammals, regardless of their personality profiles, because it has been so essential for survival. Although highly elevated levels of fear may become maladaptive in domestic environments, presumably such systems can become overactive or sensitized not only by genetic background but also by life experiences, leading, for example, to humans developing chronic anxiety/fear disorders that may need psychiatric treatments (e.g., with benzodiazepines).
CONSPECIFIC FIGHTING AND THE RAGE/ANGER SYSTEM
Even though rats have been domesticated for lab use for many generations, these animals retain a functional RAGE/Anger system and a corresponding capacity to become aggressive. However, in discussing anger, one must be careful to define the targeted behavior. While there are no selection studies based on fighting in highly domesticated lab rats, Panksepp (1971), using precise electrical stimulation of the brain, showed that like cats (Flynn, 1976; Hess, 1957b; Siegel, 2004) rats possess two separate brain systems capable of provoking an attack. One of these systems, for predatory attack, is characterized by a “quiet” systematic pursuit of mice, followed by a focused nape attack bite typically associated with predation, a behavioral trait rats commonly exhibit toward mice (Albert & Walsh, 1984). The other attack system is associated with defending resources and escaping physical restraint, such as might be experienced when caught by a predator. This latter type of “affective” attack behavior has been labeled the RAGE/Anger system (Panksepp, 1998a) and probably has evolutionary origins in the earliest vertebrates. In contrast, the predatory behavior is not generated by the RAGE/Anger system but is part of the general-process SEEKING system, which is essential for the search for food and all other resources needed for survival. Hence, what many think of as “bloodthirsty” hunting of prey is basically just finding a meal and has little to do with interpersonal violence.
Anger is an important temperament dimension, which has received more attention in animal temperament studies than in humans, especially because the Big Five personality model has relegated anger to either a “blend” or “facet” of Emotional Stability or the opposite of Agreeableness in a kind of “love-hate” dimension, rather than a separate primary personality dimension. This may also partly reflect the fact that most humans have been trained to regulate negative anger tendencies so that they rarely manifest as clearly as in animal models. However, just like the domesticated rats (which typically show little anger), humans certainly retain a powerful capacity for anger, which is all too frequently expressed in cases of domestic violence on the “full-blown” end of the anger dimension and with irritation and impatience on the more “toned-down” end.
One contribution of animal temperament research could be to help gain a better understanding of the basic brain processes underlying this primary-process emotional-temperament dimension as manifested in human personalities, which could also lead to enhanced recognition of the often hidden role of anger and milder forms of irritability in human conflict. The animal work can help pinpoint the underlying neurochemical factors that promote anger, which can lead to medicines to control this potentially dangerous aspect of human personalities. For example, as derived from animal work, antagonists of the brain neuropeptide synaptic transmitter (Substance P) that mediates animal RAGE may be helpful in regulating excessive anger/violence in human beings.
MATERNAL NURTURANCE AND THE CARE SYSTEM
A very distinctive dimension of mammalian temperament is caring for young. Michael Meaney’s group has studied maternal behavior in rats and found substantial individual differences in how rat mothers treated their newborns during their first week of life (Champagne, Francis, Mar, & Meaney, 2003). These maternal caregiving differences included the frequency and skill exhibited when licking, grooming, and nursing their neonatal pups. Remarkably, these researchers also found that individual differences in rat maternal care affected fear responses of their offspring as measured by open-field tests, amount eaten in a novel cage, and behavioral changes following a physical restraint tests. Specifically, offspring reared by mothers exhibiting less neonatal licking, grooming, and “arched-back nursing” (LG-ABN) showed increased hypothalamic-pituitary-adrenal responses to these stressors compared to offspring receiving more LG-ABN (Liu et al., 1997; Caldji et al., 1998). Cross-fostering experiments in which the rat pups of less attentive rat mothers were raised by more attentive rat mothers (Francis, Diorio, Liu, & Meaney, 1999) showed that high levels of LG-ABN decreased stress reactivity in the cross-fostered offspring, confirming that this stress resistance was indeed imparted by the effective mothering the rat pups had received. Furthermore, these maternal effects were passed from one generation of females to the next. That is, females born to less effective mothers but raised by more nurturant mothers became more effective mothers themselves. These researchers also showed that humans handling the pups of low LG-ABN mothers—more or less simulating the increased maternal stimulation—produced females whose later maternal behavior as adults was not different from those raised by high LG-ABN mothers and who exhibited increased LG-ABN toward their own neonatal pups.
In this landmark article, Meaney’s research group concluded they had demonstrated nongenomic transmission of significant individual differences of rat maternal behavior and stress reactivity (Francis et al., 1999). In other words, somehow this nurturing-evoked stress resistance was being passed on to the next generation. Subsequent research (Weaver et al., 2004) demonstrated that these epigenetic effects (more on this in Chapter 15) were the result of reduced DNA methylation in the offspring of high LG-ABN mothers. Reduced DNA methylation meant that the DNA itself was not changed, but its configuration was changed in a way that altered gene expression. Furthermore, cross-fostering could reverse the inherited genetic effect and produce a methylation pattern associated with the rearing mother (Weaver et al., 2004).
The Meaney group extended their groundbreaking research by further demonstrating that these maternally induced effects could also be reversed with fifty days of either postweaning social and environmental enrichment for offspring of low LG-ABN mothers or corresponding social isolation for offspring of high LG-ABN mothers (Champagne & Meaney, 2007). Meaney’s group has hypothesized that these epigenetic alterations may provide a means for regulating genomic expression in response to current environmental conditions reflecting different states of environmental adversity (for further discussion, see Meaney, 2010). Thus, this research group demonstrated major differences in the maternal “personalities” of rat mothers, which had real effects on how their offspring reacted to stressors in their environments. The possible implications of what this might mean for human mothering and the corresponding impact on human personalities remain to be more fully demonstrated (more on this in Chapter 15).
SEPARATION DISTRESS ENGENDERED BY THE PANIC/SADNESS EMOTIONAL SYSTEM
It is thought that rats vocalize in ultrasonic ranges that humans and most other mammals cannot hear in order to avoid detection by predators. Rat neonates emit a type of ultrasonic vocalization centered around 40 kHz that occurs in response to social isolation or cold stress and correspondingly elicits pup retrieval in mother rats (Panksepp & Burgdorf, 2000). There remains some ambiguity whether this call is evolutionarily related to the separation distress that has been more extensively studied in dogs, guinea pigs, and infant chickens, because it tends to disappear if testing is conducted in warm environments where fetal rat pups do not get cold (for critique, see Panksepp, 2003), a temperature effect that is also seen in young dogs before they are mature enough to thermoregulate.
Clearly investigators need to make better distinctions between the aversion of physical distress, such as getting cold, and the emotional distress from being separated from their mothers. True separation distress vocalizations have been associated in several species with the PANIC/Sadness system, which has been linked to depression in humans in part by the finding that opioids reduce both separation distress and human depression (Panksepp, 1998a, 2015, 2016). Infant rat data remain ambiguous on this issue. In any case, to demonstrate inherited influences on the distress vocalizations of very young infant rats, Susan Brunelli and colleagues at Columbia University selected lines of rats based on their high or low rates of such ultrasonic vocalizations in response to social isolation at ten days of age and selectively bred these lines for several generations (Brunelli, 2005). Of course, laboratory rats, because of traditional laboratory practices, are inadvertently bred to endure living in isolation (one rat per cage after weaning, typically done at three weeks of age, has long been standard practice). So Brunelli’s group started with a highly heterogeneous strain of rats from the National Institutes of Health, hoping to maximize their chances of selecting rats experiencing high levels of separation distress. In the 20th generation, there were about four times as many isolation-induced 45-kHz vocalizations in the high-vocalization line of animals compared to a randomly selected control line, which likewise exhibited substantially more 45-kHz calls than the low vocalization line, which exhibited 45-kHz calls that averaged close to zero (Brunelli & Hofer, 2007).
In the Porsolt Swim Test, an animal model for depression, the high vocalization line showed more depression-related immobile floating than did the low vocalization line, suggesting the high vocalization line represented a depressive phenotype and heightened susceptibility to stressors. However, adult rats from the high-vocalization line were also less active in the center of an open field test, suggesting higher anxiety and increased activity of the FEAR system as well. In addition, males from the low vocalization line when paired together after social isolation exhibited fighting in 70 percent of the cases, compared to 35 percent for random line males. (The high vocalization line was not included in this study.)
Brunelli and Hofer (2007) concluded that the high-vocalization line was characterized by anxiety/depression and the low-vocalization line by aggressive/impulsive behavior. Is it possible that the RAGE, FEAR, and PANIC/Sadness systems were all inadvertently influenced by their selective breeding program? As we describe in Chapter 10 with a fish selection study for aggression (Bakker, 1994), in general it seems important for investigators to have better and more comprehensive behavioral assays for the various negative emotional systems, to determine if multiple systems were changing in response to the selection procedures. For example, lowering FEAR sensitivity in the low separation distress group may contribute to higher levels of aggressiveness (as we describe with Huntingford’s fish studies in Chapter 10). Overall, it seems likely that Brunelli and her colleagues have genetically selected for high and low PANIC/Sadness sensitivity in their high and low distress vocalization lines, but it will be interesting to see in future research whether the high separation distress line would respond similarly to separation distress vocalization manipulations studied in other species, such as reduction by opioids and direct brain stimulation manipulation of key brain sites, as further evidence for the actual involvement of the PANIC/Sadness system (see Panksepp, 1998a).
Still, there are many other threads to the genetics of the personality story. Another group headed by Eva Redei at Northwestern University selectively bred two lines of rats to be either genetically susceptible or resistant to depression. Specifically, they selected sexually mature animals (seventy days old) based on their behavior in the forced swim test mentioned above. Rats that quickly gave up swimming and floated in the water were used to propagate their WMI (Wistar-Kyoto most immobile) line, with those swimming the longest selected as parents for the WLI (Wistar-Kyoto least immobile) line. By the second generation of progeny (F2s), significant differences emerged from the different parental pools (Will, Aird, & Redei, 2003). By generation twenty-two, the two lines no longer differed in their levels of anxiety as measured, for example, by activity in the center of an open field test, behavior in an elevated plus-maze, and blood levels of corticosterone after stressful restraint, all suggesting that the “behavioral differences between the two substrains of WKYs [the Wistar-Kyoto parental rats] are not fear or anxiety driven, but rather related to depressive state” (Andrus et al., 2012, p. 52).
This group then used their two selected strains to study the inborn genetic tendencies to become depressed, in contrast to depression induced by chronic stress, which they had extensively studied in various nonselected strains (see Pajer et al., 2012). In the high endogenous depression group, they identified potential biomarker transcripts (a transcript is an RNA copy of a particular DNA segment, which is copied as the first step of gene expression) in the hippocampus or amygdala, as well as in the blood samples of the WMI and WLI strains (more on similar techniques in Chapter 18 on psychopathology). They also identified transcript differences in blood samples of humans with early-onset major depression disorder versus subjects with no disorder.
In a news-grabbing finale, the Redei group was able to extend what had begun as a search for a genetic model of depression in rats—what we might call endogenous sensitivity to depression as a likely function of the PANIC/Sadness brain emotion system—into a human blood screening test for sensitivity to adult major depression disorder and possibly even the likelihood of responding to psychotherapy (Redei et al., 2014). In short, they identified nine genetic transcripts, which can be assessed in human blood samples, that distinguished depressed from nondepressed control subjects. Three of these transcripts distinguished control subjects from those with major depression even after the depression subjects had recovered. There were even gene candidates that correlated with whether depressed patients were treated successfully with therapy. Clearly, the Redei group’s research represents the value of animal research and a bottom-up approach to understanding human emotional problems. This diagnostic breakthrough is comparable to another therapeutic breakthrough that the study of animal primal emotional systems has fostered (GLYX-13), (Panksepp, 2015, 2016), which is discussed in Chapter 18.
RAT PLAY AND SEEKING SYSTEMS
If fear, anger, and social distress tendencies contribute to negativistic temperamental tendencies, the evolutionary emergence of play behavior in mammals adds a positive balance and social complexity to the domain of personality. The stable variability in playfulness among mammals suggests it is a temperamental variable, but it is a hard one to selectively breed for because it takes two animals to play, plus selection for fearfulness always reduces playfulness (Panksepp, unpublished observations). However, a new positive-affect assay for studying positive playful feelings in rats involves a human hand taking the place of a partner rat pup and simulating a “play bout” while simultaneously monitoring positive affective vocalizations that are especially common during rat pup social play (Panksepp & Burgdorf, 2000). We know these 50 kHz ultrasounds reflect positive affect because anywhere in the brain one can evoke 50 kHz ultrasonic calls with brain stimulation (mostly in subcortical sites running along the SEEKING system), animals demonstrate these states are rewarding, because they always work (self-stimulate) to obtain this positive shift in emotional state (Burgdorf et al., 2007).
Using 50-kHz ultrasonic vocalizations as an objective measure of positive social affect in these simulated play (tickling) sessions, Knutson, Burgdorf, and Panksepp (2002) selectively bred for high and low levels of this positive affective trait, yielding breeding lines that highlighted the genetic underpinning of social play (Panksepp & Burgdorf, 2003). After four generations of selective breeding, mean differences between high and low ultrasonic vocalization lines were already appearing. The high positive vocalization breeding line exhibited stronger social motivation to “play,” with shorter approach latencies and less avoidance time, than either the low vocalization or the randomly bred line of rats. The high vocalization line also exhibited more play behavior with other rats, and these rats were preferred as play partners compared to low vocalization line rat pups (Panksepp et al., 2001; Panksepp & Burgdorf, 2003).
This simulated play with a human hand—sometimes referred as “tickling”—is very rewarding to rat pups and can be used to train them to approach a hand for a tickling bout. In addition, a Pavlovian conditioning procedure demonstrated the positive reinforcement value of play tickling in that a neutral signal with no initial power to elicit 50-kHz ultrasonic “chirping”—this gleeful vocalization rat pups emit when playing—elicited the chirping after being paired with hand tickling. Highlighting the appetitive nature of this positive social affect, play deprived (socially isolated) subjects exhibited stronger conditioning than did socially housed juveniles (Panksepp & Burgdorf, 2003).
This play model has also been replicated generating new lines of high and low 50-kHz vocalizing rats (Burgdorf, Panksepp, Brudzynski, & Moskal, 2005). Again, after four generations of selection for high or low levels of the 50-kHz chirping, the high-vocalization line exhibited significantly more 50-kHz vocalizations than the other lines. In addition, research showed that negative affect 22-kHz vocalizations diverged in the opposite direction as well—happy rats complained less. Namely, they exhibited lower levels of 22-kHz distress vocalizations that have been associated with anxiety evoked by pain (Tonoue, Ashida, Makino, & Hata, 1986), addictive drug withdrawal (Mutschler & Miczec, 1998), predatory threat (Blanchard, Blanchard, Agullana, & Weiss, 1991), and social defeat (Kroes, Burgdorf, Otto, Panksepp, & Moskal, 2007). These two distinct types of ultrasonic vocalizations—50-kHz chirping versus 22-kHz distress calls—were also significantly negatively correlated in large groups of selected animals (r = –0.59, p < 0.0001; Burgdorf, Knutson, Panksepp, & Ikemoto, 2005), suggesting that the affectively positive 50-kHz vocalizations and affectively negative 22-kHz vocalizations represent polar opposite affective states in rats, confirming that these two forms of vocalizations are reciprocally related to each other (Burgdorf et al., 2001).
A variety of other emotional phenotypic differences have been evident in these replicated lines. In generation fourteen, in addition to continued playfulness and ultrasonic vocalization differences, high 50-kHz animals also exhibited diminished aggression and biting when confronted by an intruder. Also, the low 50-kHz animals behaved more like “introverts” and spent less time in contact with each other when placed in the same cage (Burgdorf et al., 2009). Perhaps the cutest finding was that young animals preferred to spend time with adults who “laughed” (chirped) a lot compared to those that laughed little (Panksepp, 2007c).
Overall, the selective breeding of highly playful rats supports the genetic basis of the PLAYful emotions within the brain. PLAY, which is the most evolutionarily recent of the six blue ribbon affective-neuroscience emotions related to personality, may also be the most complex of the six. PLAY integrates many psychological and behavioral elements providing young mammals rich social interactions and an opportunity to explore social limits in a relative safe context.
The PLAY system is indeed complex, and additional work has indicated that the 50-kHz ultrasonic vocalizations can be broken into two types. There are frequency-modulated 50-kHz calls—a kind of “trill” that covers a broader sound spectrum—that are a better measure of positive social affect than “flat” 50-kHz calls (which may be a social-sampling “hello, is anyone out there” type of call). The ability to use these frequency-modulated rat vocalizations to differentially measure positive affect has also been validated in positive anticipatory SEEKING-type situations, including food anticipation, precopulatory mating situations, and anticipation of both natural play as well as the heterospecific hand play (tickling by an experimenter). In contrast, a large variety of negative affective situations promote the 22-kHz alarm calls. Overall, this suggests these vocalizations can be used to index temperamental positive and negative affects in rats. The rewarding and punishing nature associated with these vocalizations has also been supported by operant nose poking (rat investigating activity) being increased by playback of frequency-modulated 50-kHz vocalizations and decreased by 22-kHz calls (Burgdorf et al., 2008). Again, the scientific conclusion about these calls reflecting positive affective states in animals is derived from the fact that electrical stimulation of all brain sites that generated the frequency-modulated 50-kHz trills proved to be rewarding in self-stimulation tests (Burgdorf et al., 2007). Without that kind of prediction and confirmatory data, scientists would need to keep silent about (could not draw conclusions regarding) the affective states of nonspeaking animals.
Related studies confirmed the frequency-modulated 50-kHz trills can be evoked by promoting dopamine activity, another link to the SEEKING system. Injections of amphetamine (a drug that simulates dopamine activity in the brain) into the shell of the nucleus accumbens, which is part of the mesolimbic dopamine pathway in the brain, significantly and robustly elevated the 50-kHz trills, especially in lines of rats selected for high positive affect compared to random and high negative affect lines of rats (Brudzynski et al., 2010). To further validate the neurochemical specificity of this effect and show that the increase of 50-kHz trills was mediated by dopamine, the coadministration of the dopamine antagonist raclopride attenuated the amphetamine effects, while cholinergic control drugs had no effects on these positive ultrasonic vocalizations. Indeed, because amphetamine and cocaine are addictive, it is noteworthy that the 50-kHz call can even be used as a spontaneous indicator of rats eagerly anticipating the receipt of such addictive drugs (Browning et al., 2011).
Altogether, the above findings demonstrate how easily rats can be bred to be more playful and happy, to increase play and promote high positive affect, and that dopamine has a role in enhancing this positive affect. Moreover, this work has shown that rats can indicate their affective state through emotional vocalizations provoked under standardized rat-personality testing conditions, with the 50-kHz trills reflecting a positive affective state and the 22-kHz vocalizations a negative state.
SUMMARY
In sum, yes, rats have personalities. Indeed, they exhibit complex personalities, which include expressing different levels of CAREing maternal behavior, which in turn have a direct impact on the stress tolerance of their offspring. Rats also share with cats, dogs, and other carnivorous mammals the capacity for two types of attack behavior: a predatory, quiet bite attack, which is linked to the SEEKING system, and attack behavior appropriate for defending their various resources as well as themselves, which is linked to the RAGE/Anger system.
Rats possess a complex FEAR system that psychologists have discovered is easily activated and is interwoven with all other emotional brain systems: SEEKING (curiosity), RAGE/Anger (defense), CARE (maternal nurturing), PANIC/Sadness (separation distress), and PLAY (joyful social interaction). Many times rats have been selected for high and low levels of fear expression, confirming the genetic basis of the FEAR system. Likewise, at least two labs have selected for high and low levels of PANIC/Sadness behavior, reflecting depressive tendencies. The second of these (Redei’s group; see Andrus et al., 2012) recognized the importance of ensuring that elements of FEAR did not confound the behavioral differences in their high and low depression (PANIC/Sadness) lines, which allowed them to analyze gene expression in their rat subjects and ultimately generate blood screening tests for human depression. Along similar lines, Panksepp’s group on three separate occasions has selected rats for high and low levels of PLAY behavior, which has resulted in the development of a drug to treat depression (Burgdorf et al., 2011; Panksepp, 2014; discussed further in Chapter 18).