Does Gender Matter in the Addicted Brain’s Response to Stress?

Does Gender Matter in the Addicted Brain’s Response to Stress

Men, Women, Cocaine Addiction, & Stress

Current research indicates that a person goes through three phases when developing a drug addiction and that particular brain region is associated with each phase. The first phase occurs when a person tries an addicting drug for the first time and finds that the experience feels good—perhaps uniquely good. This positive response can lead to additional experimentation with the drug and recurrent bouts of intoxication and withdrawal.

Eugene Rubin, M.D., Ph.D., is Professor and Vice-Chair for Education in the Department of Psychiatry at Washington University in St. Louis – School of Medicine.  He is also a Professor of Psychology at Washington University in St. Louis.  He is a clinical investigator in the Washington University Alzheimer’s DiseaseResearch Center, and he is involved in clinical research studying depression in the context of co-morbid medical illness.  He was the director of the psychiatry residency training program at Washington University in St. Louis School of Medicine from 1987-2007.

Editor: Nadeem Noor

This initial phase of drug abuse engages brain systems involved in motivation and reward that use dopamine as a neurotransmitter. Increasing drug use initiates a process that changes the way regions within this brain system interact with other brain regions, i.e., the degree to which one brain region is connected to another brain region is changed by the drug. These changes are associated with alterations in the physical and functional connections between nerve cells.

The second phase of addiction occurs with more regular use of the abused drug and involves changes in brain systems involved in emotion, including the amygdala and its primary connections. These regions are changed in ways that seem to make them function “normally” only when the drug is present. When the drug is absent, this emotion processing system sends out stress signals that make a person feel anxious, dysphoric, and uncomfortable. In effect, the initial phase of addiction involves the drug making a person feel good, but, with continued drug use, the disorder progresses and the drug is needed for the drug user to just feel okay.

As addiction advances to the third phase, other brain regions (for example, the prefrontal cortex) become involved in the disorder. The drug user becomes preoccupied with obtaining the drug, and behavior is dominated by drug-seeking. A person’s insight about their behavior is greatly altered. In this late phase of addiction, cognitive functions such as memory and decision-making can also be impaired.

Once a person is addicted, several factors can increase the craving for the abused drug. Some of these factors are called “drug-related cues” that remind the person about some aspect of the setting in which the drug was used. For instance, when a person addicted to cocaine is shown a picture of cocaine-related paraphernalia, he or she may feel a strong urge to use cocaine. Another group of factors leading to an increased craving for the drug involves reactions to stress. If an addicted person is confronted with something that causes him or her significant stress, this can increase the craving for the drug. These features of addiction reflect a form of drug-associated learning and involve persistent changes in brain circuitry.

Related to this discussion, a fascinating paper by Marc Potenza and colleagues recently appeared in the American Journal of Psychiatry. These investigators used a brain imaging technique called functional magnetic resonance imaging (fMRI) to identify specific areas of the brain activated during exposure to either stressful scenarios or drug-related cues. They compared the brain activity of men and women addicted to cocaine to a matched group of non-addicted research volunteers.

Do you think that the women and men addicted to cocaine showed the same pattern of brain activation when exposed to stressful scenarios versus drug-related cues? In other words, were the same changes in brain activity observed in men and women in response to these challenges?

If you answered “no,” you are correct. When shown stressful scenarios, women addicted to cocaine showed markedly increased activation of emotional regions of the brain compared to controls. Men addicted to cocaine showed very little increased activation in these emotional brain regions. In contrast, addicted men showed robust activation of brain activity in response to drug-related cues compared to controls, but women did not. Interestingly, although the pattern of brain activation in response to various stimuli was different in women and men, no gender differences were found when study participants were asked to rate the degree of their cravings for cocaine when presented with either type of stimulus.

The authors suggest that the different brain patterns observed in women and men may indicate that different strategies might be useful when treating addiction in women and men. Perhaps working on stress reduction may be more helpful when treating addiction in women and techniques to minimize responses to drug-related cues may be more therapeutic in men.

This study is important because it generates testable hypotheses that can be examined in subsequent studies. If future studies demonstrate that focusing on stress reduction in women and drug-related cues in men results in more effective treatment, then this will be an example of how modern neuroscience can improve the care of individuals with complex psychiatric disorders.

The above column was co-written by Eugene Rubin MD, Ph.D., and Charles Zorumski MD.

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