neuro
FREQUENTLY ASKED QUESTIONS
Q 01. What does your lab study?
Q 02. Why do you study addiction and depression together?
Q 03. What are reward regions?
Q 04. What are the behavioral changes associated with addiction?
Q 05. What are the behavioral changes associated with depression?
Q 06. What happens to the cells in your brain when you use a drug of abuse?
Q 07. Do these changes occur naturally in your brain without the influence of a drug abuse?
Q 08. Are the different types of addictions related? How? (Drugs, gambling, etc)
Q 09. Can the changes in your brain be reversed?
Q 10. Why do addicts relapse?
Q 11. What are transcription factors?
Q 12. What role do transcription factors play in addiction and depression?
Q 13. How do you treat depression?
Q 14. How do you treat addiction?
Q 15. What do you think is the next step in research towards the treatment of addiction?
Q 16. What do you think is the next step in research towards the treatment of depression?
Q 17. Is research into addiction and depression only about treating these disorders?
Q 18. Where can I go to find more information?


01. What does your lab study?

Our laboratory studies chemical changes in the brain that cause addiction and depression. We use animal models of these disorders to understand how drugs of abuse on the one hand, and stress on the other, change the brain to cause the behavioral abnormalities that characterize addiction and depression.


02. Why do you study addiction and depression together?

We study addiction and depression together because we believe that certain key emotional centers in the brain, called brain reward pathways, are integrally involved in both of these disorders. Drugs of abuse exert powerful effects on these reward pathways and, over time, change them to cause addiction. Likewise, we believe that many common symptoms of depression (anhedonia or loss of pleasure, loss of motivation, low energy, lack of appetite) are mediated partly by abnormalities in the reward pathways.


03. What are reward regions?

Reward regions of brain are very old from an evolutionary sense. They evolved to regulate an organism’s responses to natural rewards, like food, sex, and social interaction. These regions are critical for survival. In fact, the rudiments of the complex reward pathways found in mammals can be seen as far back on the evolutionary tree as flies and worms, which evolved ~2 billion years ago. Major reward regions of brain include the nucleus accumbens and ventral tegmental area.


04. What are the behavioral changes associated with addiction?

Addiction is characterized by a loss of control over drug use. Addicts seek and take drug despite horrendous adverse consequences; in extreme cases, the drug takes over their lives. Cues associated with drug use (friends, locations, drug paraphernalia) are powerful reminders of drug use and can induce relapse.


05. What are the behavioral changes associated with depression?

Depression is different from feeling sad, which is normal. Rather, depression is an overwhelming syndrome where feeling sad can become pervasive and is accompanied by many other symptoms, which can include: loss of enjoyment of normally pleasurable activities, too much or too little appetite, too much or too little sleep, decreased energy, and feelings of hopelessness and worthlessness, and thoughts of suicide.


06. What happens to the cells in your brain when you use a drug of abuse?

Drugs act on the brain’s reward pathways with a power and persistence not seen in the natural world. After repeated exposure, the drugs thereby change the nerve cells in these reward pathways. The cells change chemically and structurally. These changes have an overwhelming effect on the well-being of the individual: in the extreme, individuals can no longer respond normally to natural rewards (food, sex, social interaction), and instead depend on drug for such rewarding responses.


07. Do these changes occur naturally in your brain without the influence of a drug of abuse?

It is likely that similar brain changes occur in other pathological conditions which involve the excessive consumption of natural rewards, conditions such as pathological over-eating, pathological gambling, sex addictions, and so on.


08. Are the different types of addictions related? How? (Drugs, gambling, etc)

There is increasing evidence from clinical studies that some of the same brain regions (brain reward pathways) are critically involved in mediating drug addictions and the so-called natural addictions.


09. Can the changes in your brain be reversed?

There is no evidence that changes in the brain associated with drug addiction are permanent. Rather, we believe that these changes can be reversed, although this can take a long time, often many years and the reversal requires “unlearning” many of the bad habits (compulsions) associated with addiction.


10. Why do addicts relapse?

Addicts relapse for two main reasons. First, the changes that drugs of abuse produce in the brain cause very powerful biological forces that drive craving for the drug. These biological forces are hard to resist even in the context of ongoing rehabilitation treatment. Second, an addict’s life is often devastated such that they lack the social and psychological support that’s required to overcome the biological forces driving relapse.


11. What are transcription factors?

Transcription factors are proteins that bind to regulatory regions of genes and regulate the degree to which that gene is expressed.


12. What role do transcription factors play in addiction and depression?

We believe that transcription factors are key mediators of addiction and depression. Both of these disorders are associated with stable behavioral abnormalities. This stability suggests that the changes in the brain that underlie the abnormal behaviors are also stable, suggesting very fundamental abnormalities in gene expression.


13. How do you treat depression?

There are many very effective treatments for depression. Mild depression can be treated with psychotherapy or medications. More severe depression requires the use of medications. People often don’t respond to the first antidepressant medication they’re given; it’s important to keep trying different medications until some improvement is seen. Some individuals unfortunately do not respond to available treatments, which is driving research to find more effective medications.


14. How do you treat addiction?

Treatments for addiction are limited. Most efforts focus on rehabilitation, but there is a high rate of relapse. Medications that mimic drug action can be effective in helping some people avoid use of the drug. Examples include methadone and buprenorphine for opiate (heroin, morphine, etc.) addiction, and nicotine patches for nicotine addiction. Other medications blocks drug effects. The best example is naltrexone, which blocks the receptor that binds heroin. Naltrexone may also offer some benefit to alcohol and nicotine addicts; the medication blocks the receptor in the brain for endogenous opioid-like neurotransmitters, which help mediate the actions of alcohol and nicotine. However, these treatments are inadequately effective for most addicts, which highlights the great need for new medications.


15. What do you think is the next step in research towards the treatment of addiction?

We believe that an improved understanding of the neurobiology of addiction will lead to better treatments. As stated above, all available treatments for addiction either mimic or block drug action. They do not attack the changes in the brain that drive the addiction process. We need to take advantage of our increasing understanding of these changes at the molecular level to develop fundamentally new types of medications. However, even with such medications, treatment of addiction will always require psychosocial rehabilitation to repair and rebuild the addict’s life. The medications, in fact, by countering the powerful biological forces of addiction, will make such rehabilitation efforts more effective.


16. What do you think is the next step in research towards the treatment of depression?

Most available medications for depression are based on older medications introduced 50 years ago. As a result, the newer medications (like the SSRI’s or serotonin selective reuptake inhibitors) are not inherently more effective than the older medications. And they still have very troubling side effects. We need to develop antidepressants with fundamentally different mechanisms of action. And we need to develop medications that lack the side effects that dramatically limit the effectiveness of today’s medications.


17. Is research into addiction and depression only about treating these disorders?

Research into addiction and depression will not only help us understand and treat these disorders, it will teach us a lot about how the brain functions under normal and pathological conditions. This, in turn, will give us clues about many other brain disorders. In addition, the research promises to help us understand what controls the normal range of very basic behaviors, such as motivation, drive, work habits, attention, thinking, and the like. Thus, it is possible that one day this information will enable individuals to reach their maximal potential in social and occupational settings.


18. Where can I go to find more information?

See Other Sources of Information Page for links to sites that can provide more information on addiction and depression.



nestler lab
Laboratory of Molecular Psychiatry