Chapter 5. Hormones and the Brain
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Jo Marchant People with genes that make it tough for them to engage socially with others seem to be better than average at hypnotizing themselves. A study published today in Psychoneuroendocrinology1 concludes that such individuals are particularly good at becoming absorbed in their own internal world, and might also be more susceptible to other distortions of reality. Psychologist Richard Bryant of the University of New South Wales in Sydney and his colleagues tested the hypnotizability of volunteers with different forms of the receptor for oxytocin, a hormone that increases trust and social bonding. (Oxytocin's association with emotional attachment also earned it the nickname of 'love hormone'.) Those with gene variants linked to social detachment and autism were found to be most susceptible to hypnosis. Hypnosis has intrigued scientists since the nineteenth-century physician James Braid used it to alleviate pain in a variety of medical conditions, but it has never been fully understood. Hypnotized people can undergo a range of unusual experiences, including amnesia, anaesthesia and the loss of the ability to move their limbs. But some individuals are more affected by hypnosis than others — and no one knows why. Hormones and hypnotism How susceptible someone is to persuasion is an important factor in how easily they can be hypnotized by someone else. Bryant and his colleagues have previously shown that spraying a shot of oxytocin up people’s noses makes them more hypnotizable, and more likely to engage in potentially embarrassing activities such as swearing or dancing at a hypnotist’s suggestion. © 2013 Nature Publishing Group,
By Luciana Gravotta If cupid had studied neuroscience, he’d know to aim his arrows at the brain rather than the heart. Recent research suggests that for love to last, it’s best he dip those arrows in oxytocin. Although scientists have long known that this hormone is essential for monogamous rodents to stay true to their mates, and that it makes humans more trusting toward one another, they are now finding that it is also crucial to how we form and maintain romantic relationships. A handful of new studies show that oxytocin makes us more sympathetic, supportive and open with our feelings—all necessary for couples to celebrate not just one Valentine’s Day, but many. These findings have led some researchers to investigate whether oxytocin can be used in couple therapy. The first bit of evidence that points to oxytocin as nature’s love glue comes from researchers who measured the hormone in couples. Psychology professor Ruth Feldman at Bar-Ilan University in Israel, spent years studying oxytocin’s role in the mother–child bond and recently decided to dive into the uncharted waters of romantic bonds by comparing oxytocin levels in new lovers and singles. “The increase in oxytocin during the period of falling in love was the highest that we ever found,” she says of a study she and her colleagues published in Psychoneuroendocrinology. New lovers had double the amount Feldman usually sees in pregnant women. Oxytocin was also correlated with the longevity of a relationship. Couples with the highest levels were the ones still together six months later. They were also more attuned to each other than the low-oxytocin couples when Feldman asked them to talk about a shared positive experience. © 2013 Scientific American,
By Kate Clancy I tend to go to bed freezing, especially so in the winter, so I pile our flannel sheet, blanket, and down comforter over me when I settle in to sleep. A few times each menstrual cycle, clustered together in the luteal phase between ovulation and menses, I wake up from sleep completely soaked in my own sweat – not a delightful sight or experience. Usually I get up, change pajamas, and try to find a dry spot on the bed to go back to sleep (I promise the sheets eventually get washed, but I’m not about to wake my husband – and sometimes daughter – to change the bed at 3am). These night sweats started when I was still intensively breastfeeding my daughter and was marathon training, when she was under a year old. At first, I thought it was because we were co-sleeping and we slept next to each other. But I never experienced them next to my husband before that point, and he is a six foot four heat generating machine. When the marathon was over and I returned to less strenuous activity, breastfeeding frequency was also starting to decline. I didn’t get any night sweats again for quite some time. Then there was roller derby. At first, roller derby was a pastime, a recreational activity where I got to learn something totally new and hang out with women I respected. But of course, being the competitive person I am, it became an obsession, and in addition to roller derby practices I was working out quite a lot on my own time. Over the last year I’ve made additional nutritional adjustments to further improve my performance, and I’ve increased the intensity of my off-skates workouts. I work out a minimum of five hours a week, but in the middle of the season it is usually a minimum of nine hours per week. © 2012 Scientific American
Keyword: Hormones & Behavior
Link ID: 17609 - Posted: 12.17.2012
By GRETCHEN REYNOLDS Is playing football like falling in love? That question, which would perhaps not occur to most of us watching hours of the bruising game this holiday season, is the focus of a provocative and growing body of new science examining the role of oxytocin in competitive sports. Oxytocin is, famously, the “love hormone,” a brain peptide known to promote positive intersocial relations. It makes people like one another, especially in intimate relationships. New mothers are awash in oxytocin (which is involved in the labor process), and it is believed that the hormone promotes bonding between mother and infant. New-formed romantic couples also have augmented bloodstream levels of the peptide, many studies show. The original attraction between the lovers seems to prompt the release of oxytocin, and, in turn, its actions in the brain intensify and solidify the allure. Until recently, though, scientists had not considered whether a substance that promotes cuddliness and warm, intimate bonding might also play a role in competitive sports. But the idea makes sense, says Gert-Jan Pepping, a researcher at the Center for Human Movement Sciences at the University of Groningen in The Netherlands, and the author of a new review of oxytocin and competition. “Being part of a team involves emotions, as for instance when a team scores, and these emotions are associated with brain chemicals.” Copyright 2012 The New York Times Company
By Scicurious Last week, Sci covered a paper on the nematode “version” of oxytocin, nematocin, and its role in learning behavior. We usually think of oxytocin-like peptides (including oxytocin and vasopressin), as being linked with emotion, trust, love, and of course, sex. But oxytocin also tends to get a lot of hype, especially as the “love”‘ or “trust” hormone. But it’s not that. It’s much more complicated than that. And understanding the evolution of oxytocin, and its very long history, allows us to understand HOW much more complicated than that. Because while nematodes have an oxytocin-like molecule that has roles in learning behavior…well it also has roles in mating. But I wouldn’t go do far as to call nematocin (oxytocin + nematode = nematocin!) the nematode love drug. Unless, of course, you believe nematodes have deep, passionate, trusting, and communicative one-night worm stands which commence upon immediate contact and end immediately after. Hey, you never know. This happens to be an interesting issue of Science, in which TWO papers were published, both identifying nematocin, at the same time. As they both call the new molecule nematocin, I have hopes that the two groups were happily collaborating with each other to further the interests of science (though I know that many times, when two groups find the name new, hot thing, it’s often a very bitter race to publish). So what is nematocin? Nematocin appears to be a chemical closely related to oxytocin and vasopressin, those much vaunted chemical in mammals which are making so much press for their role in our emotions and moral behavior. But oxytocin and vasopressin are both more complicated than emotion. Vasopressin, for example, plays a role in water balance. And it appears that the newly discovered nematocin in the nematode C. elegans may be similar, with more than one role in more than one system. © 2012 Scientific American
By Laura Beil Kotex, the company that first capitalized on the concept of “feminine hygiene” more than 90 years ago, recently gained newfound success after it began targeting an underserved market: girls who start their periods before they start middle school. With hearts, swirls and sparkles, the U brand offers maxi pads and tampons for — OMG! — girls as young as 8, promoted through a neon-hued website with chatty girl-to-girl messages and breezy videos. “When I had my first period I was prepared,” reads one testimonial. “It was the summer before 4th grade….” Today it has become common for girls to enter puberty before discovering Are You There God? It’s Me, Margaret. Over the second half of the 20th century, the average age for girls to begin breast development has dropped by a year or more in the industrialized world. And the age of first menstruation, generally around 12, has advanced by a matter of months. Hispanic and black girls may be experiencing an age shift much more pronounced. The idea of an entire generation maturing faster once had a strong cadre of doubters. In fact, after one of the first studies to warn of earlier puberty in American girls was published in 1997, skeptics complained in the journal Pediatrics that “many of us in the field of pediatric endocrinology believe that it is premature to conclude that the normal age of puberty is occurring earlier.” Today, more than 15 years later, a majority of doctors appear to have come around to the idea. Have a conversation with a pediatric endocrinologist, and it isn’t long before you hear the phrase “new normal.” © Society for Science & the Public 2000 - 2012
By Melissa Healy, Los Angeles Times If retired Army Gen. David H. Petraeus had gotten an occasional dose of supplemental oxytocin, a brain chemical known to promote trust and bonding, he might still be director of the Central Intelligence Agency, new research suggests. A study published Tuesday in the Journal of Neuroscience has uncovered a surprising new property of oxytocin, finding that when men in monogamous relationships got a sniff of the stuff, they subsequently put a little extra space between themselves and an attractive woman they'd just met. Oxytocin didn't have the same effect on single heterosexual men, who comfortably parked themselves between 21 and 24 inches from the comely female stranger. The men who declared themselves in "stable, monogamous" relationships and got a dose of the hormone chose to stand, on average, about 6 1/2 inches farther away. When researchers conducted the experiment with a placebo, they found no differences in the distance that attached and unattached men maintained from a woman they had just met. Even when an attractive woman was portrayed only in a photograph, the monogamous men who received oxytocin put a bit more distance between themselves and her likeness. But when the new acquaintance was a man, administration of oxytocin did not prompt attached men to stand farther away than single men, the researchers reported. Los Angeles Times, Copyright 2012
by Andy Coghlan Men with partners increase the space they feel comfortable with between themselves and an attractive woman if exposed to the bonding hormone oxytocin. René Hurlemann at the University of Bonn in Germany and colleagues gave men either a sniff of oxytocin or a placebo before asking them to choose the ideal distance for an interaction with a woman. The distance that they felt was comfortable significantly increased after sniffing oxytocin, but only for men in relationships. The team conclude that oxytocin discourages partnered but not single men from getting close to a female stranger. Journal reference: Journal of Neuroscience, DOI: 10.1523/jneurosci.2755-12.2012 © Copyright Reed Business Information Ltd.
by Shaoni Bhattacharya Talk about having your cake and eating it. Fasting might not be the only route to a longer life – a hormone seems to work just as well, for mice at least. We know that some animals can extend their lifespan by consuming fewer calories. Engineered mice can get the same effect by simply pumping out high levels of a hormone normally produced during a fast, according to Steven Kliewer and David Mangelsdorf at the University of Texas Southwestern Medical Center in Dallas. Their team found that mice engineered to make higher levels of the hormone, FGF21, increased their lifespan on average by over a third. "What we are seeing is the benefit of caloric restriction without having to diet," he says. Humans have the hormone too, and Kliewer believes FGF21 has the potential to extend the human "health-span" – the time we live healthy lives. The researchers believe FGF21 may act to prolong life by affecting pathways such as the insulin-like growth factor-1 (IGF-1) pathway implicated in ageing. "It blocks growth hormones promoting pathways which are associated with diseases, including cancers and metabolic diseases, and as a consequence these animals live longer," says Kliewer. © Copyright Reed Business Information Ltd.
Researchers in the U.S. have found signs of puberty in American boys up to two years earlier than previously reported — age nine on average for blacks, 10 for whites and Hispanics. Other studies have suggested that girls, too, are entering puberty younger. Why is this happening? Theories range from higher levels of obesity and inactivity to chemicals in food and water, all of which might interfere with normal hormone production. But those are just theories, and they remain unproven. Doctors say earlier puberty is not necessarily cause for concern. And some experts question whether the trend is even real. Boys are more likely than girls to have an underlying physical cause for early puberty.Boys are more likely than girls to have an underlying physical cause for early puberty. (Jennifer DeMonte/Associated Press) Dr. William Adelman, an adolescent medicine specialist in the Baltimore area, says the new research is the first to find early, strong physical evidence that boys are maturing earlier. But he added that the study still isn't proof and said it raises a lot of questions. Earlier research based on 20-year-old national data also suggested a trend toward early puberty in boys, but it was based on less rigorous information. The new study involved testes measurements in more than 4,000 boys. Enlargement of testes is generally the earliest sign of puberty in boys. The study was published online Saturday in Pediatrics to coincide with the American Academy of Pediatrics' national conference in New Orleans. © CBC 2012
By Marcia Malory Ask this question, and you will probably receive one of two responses: Yes. People choose to be gay. They are making an immoral choice, which government should discourage. Or No. Sexual preference is biologically determined. Government should protect gay people from discrimination because homosexuality is an unalterable aspect of their identity. These two answers have something in common: With both of them, the science conveniently supports the moral decision. What if neither answer is right? Perhaps sexual preference can be changed – and people have the right to engage in gay sex and have homosexual relationships if they choose to do so. (The fourth option, that gay people have no choice but to be gay, but should be punished for it anyway, is morally unthinkable.) What does science tell us about sexual preference? We know, from many twin and adoption studies, that sexual preference has a genetic component. A gay man is more likely than a straight man to have a (biological) gay brother; lesbians are more likely than straight women to have gay sisters. In 1993, a study published in the journal Science showed that families with two homosexual brothers were very likely to have certain genetic markers on a region of the X chromosome known as Xq28. This led to media headlines about the possibility of the existence of a “gay gene” and discussions about the ethics of aborting a “gay” fetus. © 2012 Scientific American,
By Tina Hesman Saey New work suggests that a hormone that makes the body think it’s starving could prolong life about as long as severely cutting calories does but without the denial. A hormone called fibroblast growth factor-21, or FGF21, lengthened the lives of mice that had been genetically engineered to constantly produce large amounts of the protein, researchers at the University of Texas Southwestern Medical Center at Dallas report online October 15 in eLife. The hormone is normally made by the liver during fasting and may tap into some of the same life-extending biochemical processes as does caloric restriction, a proven longevity booster. Caloric restriction — usually defined as cutting calorie intake to 75 to 80 percent of the amount needed to maintain normal body weight, while still maintaining good nutrition — has been shown lengthen life in a wide variety of species, such as fruit flies and dogs. Minimal calorie consumption turns on many different biological processes that slow aging, says Cynthia Kenyon, a developmental biologist at the University of California, San Francisco. The hormone in the study somehow interferes with a chain reaction anchored by insulin-like growth factor-1 (IGF-1), a process that is also shut down by caloric restriction and thought to be responsible for many of its life-extending effects. In the study, researchers led by UT Southwestern’s David Mangelsdorf and Steven Kliewer genetically engineered mice to constantly make five to 10 times as much FGF21 as normal. These engineered mice lived 30 to 40 percent longer than normal mice on a standard diet. Female mice benefitted from the hormone even more than males; about a third of the FGF21-producing female mice still were alive at 44 months old. Average survival for normal mice in the study was about 28 months. © Society for Science & the Public 2000 - 2012
By Gary Stix First off, this study on a molecule tied to social interaction was conducted in animals. So I’m supposed to turn on the siren and the flashing red light here to let you know that the headline you just read might not apply in humans. Still, the animals in question, prairie voles, are a special case, models of faithfulness that put humans to shame when it comes to the delicate topic of monogamy. Once hitched, the rodents stick with their mates for life—an example of moral pulchritude in the animal kingdom that many of us human sinners can never hope to emulate. It could easily become the state animal for whole regions of the U.S. For just that alone, the implications of the experiment in question are particularly intriguing. The new research shows that oxytocin, the bonding hormone, is sometimes capable of turning the upstanding rodent into an anti-social lout, making the study results more compelling in many ways than if they were reported in errant humans. So the man-bites-dog headline stays. This all came up when Karen Bales, a professor at University of California, Davis, wanted to know what would happen if oxytocin gets administered for lengthy intervals, not the short-term dosing that has occurred in the multitude of previous vole studies that linked the hormone to monogamous behavior. In their experiment, Bales and team gave either a low, medium or high dose through the nose to 29 voles, and a saline solution to 14 controls At first, the animals became all cuddly as in previous studies But after three weeks, an entire vole childhood (from weaning to sexual maturity), they started breaking bad. Males did not engage in the normal behavior of “pair bonding,” that drives them to look for the girl of their dreams. And female voles’ natural mothering instinct seemed to disappear: when placed nearby young pups that were not their own, they didn’t dote, as they are wont to do. The cuddle hormone had turned the rodents into meanies. © 2012 Scientific American
(Relaxnews)—In a study of more than 90 men, scientists from the University of Bonn, Germany, found that subjects treated with a dose of testosterone before the study told fewer lies than those who received a placebo. "Testosterone has always been said to promote aggressive and risky behavior and posturing," says researcher and neuroscientist Bernard Weber. However, more recent studies indicate that it also fosters social behavior. Prior research has suggested that the hormone may actually cause people to be more "prosocial" in that they voluntarily act in the interest of others, writes the Atlantic magazine, but exactly how the hormone influences behaviors isn't understood. For this latest study, 46 subjects were treated with testosterone by applying it to the skin in gel form, while 45 subjects received a placebo. The next day, the subjects played a dice game in which it was easy for the men to lie to earn more money, with no possibility of being caught. The study was designed so that it was impossible even for the researchers to detect whether a subject was lying or not. Rather, they used statistics to analyze reported earnings that were higher than probability would allow, inferring from these how honest the subjects were being. While many people in the study lied about the game, there was a noticeable difference between the men boosted with testosterone and those who weren't—the testosterone group avoided the temptation to cheat more often. Blood tests confirmed the results that high testosterone levels were linked with more honest game playing. "Test subjects with the higher testosterone levels had clearly lied less frequently than untreated test subjects," says co-author Armin Falk. "This result clearly contradicts the one-dimensional approach that testosterone results in anti-social behavior." The study was published last week in the journal PLoS One . http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046774 © 2012 NY Times Co.
Keyword: Hormones & Behavior
Link ID: 17378 - Posted: 10.17.2012
Cort Pedersen at the University of North Carolina at Chapel Hill and his team gave 11 alcohol-dependent volunteers two daily doses of an oxytocin nasal spray or a placebo, during the first three days of a detox programme. The volunteers also received lorazepam - a detox drug - when their withdrawal symptoms reached a specific level. The oxytocin group had fewer alcohol cravings and milder withdrawal symptoms than the placebo group, and used just one-fifth of the lorazepam (Alcoholism: Clinical and Experimental Research, doi.org/jgp). "Four [oxytocin] volunteers didn't need any lorazepam at all," says Pedersen. This is good news because lorazepam is highly addictive. While it reduces anxiety and seizures during alcohol withdrawal, users can experience insomnia and cravings when they come off the drug. Although it is unclear how oxytocin - famed for its role in social bondingMovie Camera - helps to aid withdrawal, it has no known side effects. Pedersen hopes that alcoholics who take the hormone will therefore be less likely to experience the unpleasant symptoms that can lead to relapse. © Copyright Reed Business Information Ltd.
by Gisela Telis In the industrialized world, women live at least 5 years longer, on average, than men. Scientists have attributed that difference to everything from healthier habits to hardier cells. Now, a new study that analyzes the longevity of eunuchs, or castrated men, suggests that testosterone may play a part in shortening men's lives. The idea that testosterone, the male sex hormone, affects lifespan isn't new. Neutered dogs and other animals that have had their sources of testosterone removed often live longer than their intact counterparts. But studies on the connection between castration and longevity in humans are harder to come by, and the results have been inconclusive. A 1969 study of institutionalized patients in Kansas found that castrated men lived an average of 14 years longer than other men in the same facility, but a 1993 study of Italian castrati (singers castrated as boys to preserve their high voices) found nothing unusual about their longevity. Almost 5 years ago, biologist Kyung-Jin Min of Inha University in Incheon, Korea, found himself considering this lack of data while watching a Korean TV drama about eunuchs. Min began to wonder if Korea's rich historical records could shed light on the link between castration and longevity in humans. Until the late 19th century, Korean rulers employed eunuchs to serve the royal court. These eunuchs were allowed to marry and adopt castrated boys as their sons. The Yang-Se-Gye-Bo, a genealogical record of the eunuch families, has survived, and it documents the birth and death dates and other personal details of 385 eunuchs who lived between the mid-16th century and the mid-19th century. © 2010 American Association for the Advancement of Science.
By Judy Stone In one sense, it is refreshing to see men being the target of pharma, after all these years of women being the focus of relentless—and misleading—advertising. On the other, we’re seeing the start of yet another pharma campaign to dupe the public by the unnecessary medicalization of symptoms to create new drug markets. I used to be a fairly enthusiastic pharma fan, but over recent years have become increasingly disillusioned. The hype over testosterone is the latest example of why. With so many pressing problems in the world, I wish pharma would focus their attention on doing something more useful with their energies. I thought it started with drugs for “hot flashes,” but Karen Roush set me straight about hormone therapy, reporting that “It all started with men in ancient civilizations eating the penis and testicles of animals as a cure for impotence.” (And to think that Maryn McKenna just warned us of the dangers of kissing cats! This early hormone therapy sounds a bit dicier.) In the 1940s, estrogen was able to be extracted from horse urine in large quantities, enabling a supply for treating women “suffering from estrogen deficiency.” Dr. Robert Wilson, a prominent New York gynecologist, founded a private trust in 1963 to promote estrogen use. Pharmaceutical companies provided $1.3 million to this “trust;” they, of course, stood to profit handsomely from their investment in Wilson’s endeavor. Wilson is described as being “evangelical” in his crusade to save women from the “decay” of menopause. He was quite successful, with his 1966 book, Feminine Forever, selling 100,000 copies in the first seven months alone. His theme, “A Plea for the Maintenance of Adequate Estrogen from Puberty to Grave,” expounded in a mainstream medical journal, was adopted both by the medical profession and by the popular press. © 2012 Scientific American
By GRETCHEN REYNOLDS It’s widely accepted among scientists that regular exercise transforms the brain, improving the ability to remember and think. And a growing and very appealing body of science has established that exercise spurs the creation of new brain cells, a process known as neurogenesis. But just how jogging or other workouts affect the structure of the brain has remained enigmatic, with many steps in the process unexplained. A new study published last month in Proceedings of the National Academy of Sciences may fill in one piece of the puzzle, by showing that male sex hormones surge in the brain after exercise and could be helping to remodel the mind. The research was conducted on young, healthy and exclusively male rats – but scientists believe it applies to female rats, too, as well as other mammals, including humans. The decision to use only males was carefully considered. “We’ve known for a while that estrogen,” the female sex hormone, “is produced in the brain” not just of female animals but also, to some degree, in males, says Bruce S. McEwen, the director of the Laboratory of Neuroendocrinology at Rockefeller University in New York and an author of the study, which also involved scientists from the University of Tsukuba in Japan and other institutions. Estrogen has been well studied and has many effects, he said, including, scientists suspect, new brain cell growth. But far less has been known about the role of male sex hormones in mammalian brains, particularly after exercise. While both sexes produce male sex hormones, males produce far more of it – mostly in the gonads but, the researchers suspected, also in the brain. Copyright 2012 The New York Times Company
By Matthew Perrone, Associated Press "Do you have a decrease in libido?" "Have you noticed a recent deterioration in your ability to play sports?" "It could be Low-T." Welcome to the latest big marketing push by the nation's drug companies. In this case, it's a web page for Abbott Laboratories' Androgel, a billion-dollar selling testosterone gel used by millions of American men struggling with the symptoms of growing older that are associated with low testosterone, such as poor sex drive, weight gain and fatigue. Androgel is one of a growing number of prescription gels, patches and injections aimed at boosting the male hormone that begins to decline after about age 40. Drugmakers and some doctors claim testosterone therapy can reverse some of the signs of aging — even though the safety and effectiveness of such treatments is unclear. "The problem is that we don't have any evidence that prescribing testosterone to older men with relatively low testosterone levels does any good," says Dr. Sergei Romashkan, who oversees clinical trials for the National Institute on Aging, a part of the National Institutes of Health conglomerate of research centers. Low testosterone is the latest example of a once-natural part of getting old that has become a target for medical treatment. Bladder problems, brittle bones and hot flashes have followed a similar path: from inconvenient facts of life, to ailments that can be treated with drugs. The rise of such therapies is being fueled by both demographics and industry marketing. © 2012 NBCNews.com
By Scicurious We’ve all heard of the legendary monogamous prairie vole, haven’t we? Our adorable rodent friend forms the kind of attachments that make us humans feel slightly ashamed of our more promiscuous habits. And of course, if we know about prairie voles, we know about oxytocin (and I’ve got a whole series on it over at the ‘Science! 101′ page of my other site). Prairie voles are monogamous primarily due to the actions of oxytocin in the female, and vasopressin in the male. Without these two hormones, the prairie voles will love ‘em and leave ‘em just like their close cousins, the meadow vole. But is that all there really is to pair bonding? Just one hormone, a desire to stay with your furry mate forever…and that’s it? No, it’s more complicated than that. There are two real aspects to a pair bond. The first is the prosocial bit, the animal preferring to associate with one particular other animal. In voles, this requires the hormones oxytocin and vasopressin, and the neurotransmitter dopamine. But there’s another aspect to pair bonding: maintenance. And that requires more than fuzzy feelings, it also requires rejection of other potential mates, and guarding your mate against all comers. This aggressive behavior also involves dopamine, but in this case, a different population of receptors. © 2012 Scientific American