The Brain Wave: Neurogenesis as treatment for drug addiction

Drug abuse is a major societal problem. According to the National Institute of Drug Abuse, substance abuse imparts an annual economic burden of more than $600 billion. In particular, cocaine is a powerful stimulant that can cause severe medical consequences, such as heart attacks and strokes. Currently, there is no single medication that can treat cocaine addiction, and psychosocial therapies are often not effective in a significant population of cocaine abusers. Research into how drugs affect the brain is crucial for development of better therapies to reverse addiction and prevent relapse. The most studied cocaine mechanism is how the drug affects the brain’s reward pathway. The reward pathway is a system of neural circuitry that allows us to associate beneficial behaviors with feelings of pleasure. The neurons that are responsible for pleasure form a group called nucleus accumbens (NAc). NAc neurons are activated by a chemical called dopamine, which is released by ventral tegmental area (VTA) neurons. Under normal conditions, the reward pathway is kept in check by the dopamine transporter, which brings back excess dopamine inside the cell. Scientists believe that cocaine produces its addictive effects by blocking these dopamine transmitters, leading to a buildup of dopamine that is responsible for the intense feelings of pleasure and euphoria. Although the reward pathway is an attractive drug target, prevention of abuse is still preferable to treating an already formed addiction. Even if treatment is successful, almost of half of cocaine users will relapse within two and a half months. As a result, identifying risk factors for drug abuse is a critical area of research that will set the stage for strategies to prevent addiction. Outside of the reward pathway, cocaine has been shown to induce changes in the brain’s plasticity. One form of plasticity is neurogenesis (the creation of neurons), which occurs in the hippocampus even during adulthood. What is important to realize is that adult neurogenesis is an elaborate biological pathway in which neural stem cells proliferate to produce neuroblasts, which then migrate and differentiate into newborn neurons. Moreover, the newborn cells have to survive long enough to be able to integrate into preexisting circuitries. Studies have shown that administration of cocaine to rats decreases cellular proliferation in the hippocampus, whereas cocaine’s effect on long-term survival is still unclear. Regardless, these studies at least show that cocaine addiction and decreased neurogenesis appear to be correlated, suggesting a possible role of neurogenesis in the development of cocaine abuse. To investigate the causal role of neurogenesis in drug addiction, one study reduced hippocampal neurogenesis by exposing rats to radiation. The study found that inhibition of adult neurogenesis increased cocaine-seeking behavior and likelihood of relapse. These findings were the first to show that the manipulation of neurogenesis could be an effective strategy in preventing drug abuse behavior. More specifically, increasing neurogenesis could perhaps prevent cocaine addiction. So far, no published study has examined this possibility. Given that there are mice genetically engineered to have more neurogenesis than normal, we can easily test the hypothesis that increasing neurogenesis may prevent cocaine abuse. Why might a decrease in neurogenesis contribute to addiction behavior? Cocaine can rewire the brain through a variety of pathways, and a decrease in neurogenesis could represent changes in neural plasticity that reinforces addiction behavior. Some reports have shown that cocaine can cause neuronal loss, and thus increasing neurogenesis can boost the body’s endogenous regenerative mechanism to compensate for damaged circuits. Additionally, it is known that stress can also reduce neurogenesis. Given that depressed individuals are more vulnerable to drug addiction, decreased neurogenesis might simply be a reflection of stress that puts individuals at risk for drug abuse. Regardless of my interest in neurogenesis, I don’t think that focusing only on neurogenesis will solve the drug addiction problem, given the multitude of other brain processes involved. I envision that a future treatment might be a combination of both social counseling and medications that target multiple neuronal underpinnings of drug addiction. However, a better understanding of how neurogenesis contributes to drug abuse may lead us toward a greater insight into how neurogenesis participates in brain function.