Gender Specific Mechanisms for Understanding Smoking Addiction
Irina Esterlis, Ph.D., Assistant Professor of Psychiatry
Nicotine replacement therapies - the most commonly used treatments for quitting smoking - are not as effective for women as for men. Thus, to improve cessation therapies for women, there is a critical need to investigate whether the neurobiology of smoking in women is different from that targeted by the therapies that affect nicotine receptors in the brain. By using PET scanning (a technology that produces visual images of cellular and molecular level functioning), Dr. Esterlis is taking the first steps in investigating whether treatments targeting brain receptors - called metabotropic glutamate receptors (mGluR5) - may be a better option for helping women quit smoking. She believes glutamate receptors are excellent candidates because evidence from animal studies suggests gender differences in the role of mGluR5 in nicotine addiction, and glutamate, a key chemical messenger in brain cells, has been shown to be compromised in mood disorders such as depression, one of the reasons that women smoke or relapse to smoking after quitting.
This study is funded in conjunction with the Yale Comprehensive Cancer Center.
Determining Genetic Factors that Contribute to Alcoholism in Women
Jaakko Lappalainen, M.D., Ph.D., Assistant Professor of Psychiatry
Alcoholism is common, debilitating and genetically influenced. A portion of the genetic risk is due to genes that affect primarily women, but not men. Dr. Jaakko Lappalainen pursued the identification of sex-specific genes in order to understand the development of alcoholism in women, and facilitate treatment and prevention strategies for women and men.
Highlighted Study Findings
Genetic research requires systematic testing of specific genes to determine the impact of genetic contributions to any given disorder. Previous research suggests that genetic factors involved in the risk to develop alcoholism may be sex-specific, in that either women may have different genes than men that predispose them to alcoholism or the effect of the same genes may be different in women and men. The success of this project is found in ruling out specific genes that were believed to have an impact on alcoholism in women. Dr. Lappalainen’s results also contributed to an increase in public awareness about the impact of biological factors on alcoholism, often considered a condition with solely behavioral etiologies.
Pilot Project Study was funded in 2001, Dr. Lappalainen is now in Delaware
Studying the Molecular Basis for Sex Differences in Depression and Nicotine Addiction
Marina R. Picciotto, Ph.D., Associate Professor of Psychiatry, Pharmacology and Neurobiology
Depression is more common in women than men, and cigarette smoking is far more prevalent in those with depression (40-60%) compared to the general population. Further, there are distinct differences in smoking behaviors for women versus men, including the fact that it is more difficult for women to quit smoking. The goal of Dr. Picciotto’s research was to begin to understand the relationship between depression and smoking as two inter-related health concerns for women.
Highlighted Study Findings
The interaction of brain chemistry and sex hormones (such as estrogen) likely play an important role in the sex differences seen both in depression and smoking behavior. Dr. Picciotto and her laboratory found that certain molecular structures in the brain implicated in depression are also responsive to the pleasant effects of nicotine, suggesting that smoking may be used to decrease depressive symptoms. Interestingly, female, but not male, mice preferred to drink a nicotine solution rather than water, perhaps indicating that female mice are more sensitive to nicotine. Further, mice who had their ovaries removed no longer preferred nicotine, suggesting that sex-specific hormones such as estrogen, may be important in maintaining smoking behavior. Taken together, these findings suggest that nicotine-responsive molecular structures in the brain affect both smoking behavior and depressive symptoms, and demonstrate that nicotinic receptors are a novel target for development of antidepressants. This development is now under way.
Understanding Sex Differences in Motivation and Control with Regard to Drug Use
Jane R. Taylor, Ph.D., Associate Professor of Psychiatry
Emerging findings suggest that women, compared to men, have increased sensitivity to the behavioral effects of stimulants, including cocaine and nicotine. Despite drug use being more prevalent in men, women become more rapidly dependent on these substances and are more likely to have predisposing psychiatric disorders, such as depression. However, the reasons for these gender differences are not fully understood. Against this backdrop, Dr. Taylor studied whether female animals are more likely than male animals to relapse to drug use after being stressed or being exposed to drugs of abuse.
Highlighted Study Findings
In her study, Dr. Taylor investigated how motivational processes in female animals are affected by stress and by psychomotor stimulants. She also examined sex differences in impulsiveness and cognition using animal models of attention. She found that both "stressed" female rats and those having received drugs of abuse (such as cocaine, amphetamine or nicotine) are more sensitive to cues associated with "rewards" for behavior. These findings suggest that females may be more prone to relapse to drug use when provoked by stress or re-exposure to drugs than males because they are seeking the “rewarding" properties of drugs. Interestingly, female rats showed reduced impulsivity in tests of sustained and divided attention compared with male rats, effects that are important for normal cognitive performance. These findings are consistent with the high incidence of attention loss in disorders such as attention deficit/hyperactivity disorder (ADHD), which is more prevalent in males compared with females. The results also suggested that estrogen may protect aspects of cognitive function. These data are important steps toward creating a basis for developing novel gender-based pharmacological and behavioral treatment strategies for drug addiction, as well as for hormonal treatment as part of therapy.