wellness

hard wired
U.Va. woman researcher delves deep into what causes our cravings
By M. Grace Maselli
brain circuitry. Females who abuse substances are more likely to become dependent on them compared to men because they require less exposure. And it may be harder for them to become free of drugs, she says. According to Lynch, the neurotransmitter dopamine is a major player in this scenario. Dopamine fires a signal to a cell by way of a neuron in a process known as synapse. Females have a greater increase in dopamine compared to males in the reward section of the brain, says Lynch. Its this reward section or pathway, also known as the Nucleus Accumbens, a smallish area behind the brains Prefrontal Cortex, that gets aroused when your eyes land on an upscale pair of designer boots or your senses acknowledge the first swirl of Chardonnay in a glass, or a line of cocaine on a table. The Nucleus Accumbens goes wild and dopamine starts to accumulate, Lynch explains. Dopamine is also a confounding neurotransmitter for other reasons. Weve tested many different dopamine-type drugs and they dont work, Lynch says. In the initial, flirtatious stages of addiction, dopamine responds with complete, full-steam-ahead ardor in the brain, signaling intense pleasure in the reward section. But once someone is addicted, they dont feel as good when they use because theyre no longer getting the same level of dopamine response. We dont know yet why this happens, Lynch says. Glutamate, another neurotransmitter in the brain, is likewise being researched in Lynchs lab. Glutamate also sends signals to the brains Nucleus Accumbens to activate the reward pathway, so were also looking at ways to modulate this signaling to control addiction in men and women, Lynch explains. Drug addiction is complicated because there are a lot of different neurotransmitter pathways in the brain that are affected by it, offers Susan Doyle, Ph.D., and a research scientist who oversees cocaine addiction projects in the Lynch lab at the University of Virginia. Binging, withdrawal, and relapse are the behaviors that describe the classic movement for women and men through phases of addiction, or what Doyle describes as a vicious cycle. And though the published research demonstrates that women

Have you ever really craved a glass of Cabernet, or a piece of chocolate, or a beautiful pair of shoes? (Thank you Sex and the City for expanding our collective and precious awareness of Manolo Blahnik footwear in the universe.) The euphoria you feel from that rush of alcohol, sugar or the plunge into exotically soft and expensive leather may have much more to do with your neurobiological wiring than you think. Maybe even particularly so because youre a woman. Wendy Lynch would know. A research scientist and associate professor at the University of Virginia, Lynch heads the research lab in the Department of Psychiatry and Neurobehavioral Sciences, and has devoted her career to trying to unlock the mysteries behind the pathology of addiction. Lynchs lab is in the research vanguard because it explores women in particular, and how their brains shift in the shadow of addiction to determine potential treatmentsand for identifying men and women who are at risk for addiction. Were learning that women are more vulnerable to addiction than men, says Lynch, a Ph.D. from Yale University and a research scientist for 1 years. Though historically men are more likely to use and abuse drugs. Or entangle themselves in harmful ways with other flavors of addictions: compulsive gambling, sex obsessions, getting hooked on the Internet, and arguably an unhealthy preoccupation with the TV remote. Behaviorally speaking, whats new for women, Lynch says and more alarmingly, for adolescent girls, in particular is that the social stigma attached to drug use is much less so, which means there are greater numbers of females than ever before using drugs and engaging in other forms of addictive behavior. The lowered bar on acceptance of these behavioral transgressions, or however you want to define it, isnt the only culprit. The more widespread acceptance of nicotine, cocaine and alcohol use, along with other forms of substance abuse among women and girls, is the vulnerability to addiction encoded in their
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Photo by Terry Beigie

get hooked and relapse faster than men on a substance like cocaine, they also seek help more quickly. Women will relapse for reasons associated with stress and depression, the negative effects in life, Doyle says. Conversely, men report more positive experiences before relapse, she says. Some of the most hopeful news is that the work being done in the Lynch lab has direct clinical application. The goal of my research is to tease apart the neurobiological processes that are different between women and men to development the most effective addiction treatments, says Doyle. Although statistics are greater for numbers of addicted men compared to women, women are faster than men at becoming addicted to drugs and other repetitive behaviors like gambling. So the fear is that over time the quantity of female addicts will increase, says Lynch who, besides teaching classes in neuroscience and writing grants for her lab, is a devoted mentor to her neuroscience students, upwards of 10 at the moment making their way through the Ph.D. and undergraduate programs. Im a scientist whose job is to mentor students so they know how to collect and analyze data. I teach them how to write, to be enthusiastic and to study addiction, Lynch says of her program designed to extend academic opportunity to under-represented and minority students who are often first-generation college students. Alexis Peterson is a second-year neuroscience graduate student in Lynchs lab. In my work right now Im looking at the efficacy of non-pharmacological intervention in an animal model of cocaine addiction, explains Peterson. By non-pharmacological, she means the work shes doing that specifically looks at exercise as a treatment during drug withdrawal and its effect on cocaine relapse in females and males. Our studies with rats lead us to believe that females who have access to exercise are less likely than males to seek cocaine, says Peterson, whose favorite course is a weekly student seminar for graduate students to present their research data and engage in lively discussion. We get to ask a lot of questions and the process teaches us how to give formal lectures, she says. Somewhat optimistically, there is a brighter side when it comes to taking charge of uncontrollable cravings. It has to do with a double-edged sword known as hormones. Estrogen, a female sex hormone that dips radically during pregnancy, makes us vulnerable to addiction by increasing dopamine in the brain, explains Lynch. Conversely, another naturally occurring hormone, progesterone, famous for its inextricable link to womens menstrual cycles and its skyrocketing increase in the body during pregnancy, may have some benefit when it comes to warding off drug addiction, though any silver bullet in the world of addiction research is unlikely, Lynch says.

Progesterone is being studied as a form of drug protection against addiction for women as well as men, says Lynch. Were using progesterone with some success as an addiction treatment for smoking and cocaine. It shows some real promise, she adds. Given societys expectations of mens masculine image, Lynch says, shes reluctant to talk to men about using a female sex hormone as a treatment typedespite how good the data on progesterone may look. Its promise notwithstanding, progesterone alone wont cure anybody, Lynch believes. Another positive for women regarding addiction, says Lynch, whose research lab is predominantly made up of females, is that women also have the benefit of being protected by socio-cultural factors. After child birth there are more social responsibilities competing for a mothers attention. The choices are to either take care of your kids or do drugs. And progesterone may protect individual women long term against loving drugs, she says. Once we figure out how the brain changes after addiction, then its easier to understand how we reverse the brains circuitry, Lynch offers, speculating, maybe the cure is a blend of environmental antidotes, like exercise, combined with a range of low-dose medicines? la the pharmacological cocktail blend associated with HIV drug treatment. The right solution will have wide-ranging implications not only in scientific terms, but sociological and perhaps more, Lynch asserts, After all, wouldnt it would be profound if addiction no longer had the power to destroy families?
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