Can Memantine Treat Compulsive Behaviors in Adolescents?

What you need to know

• Compulsive behaviors often develop during childhood and can be difficult to treat
• This study tested if memantine, a drug that affects glutamate in the brain, could reduce compulsive behaviors in adolescent rats
• Memantine did not reduce compulsive behaviors or change brain connectivity in this rat model
• The lack of effect may be due to interactions between memantine and the drug used to induce compulsive behaviors in the rats
• More research is needed to understand if memantine could potentially help treat compulsive behaviors in humans

Understanding compulsive behaviors

Compulsive behaviors involve repetitive actions that someone feels they must do, even if they don’t want to. These behaviors are common in conditions like obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD). Compulsive behaviors often start during childhood or the teenage years.

Current treatments, like certain antidepressants and behavioral therapy, can help some people. However, many individuals still struggle with compulsive behaviors even with treatment. This highlights the need for new treatment approaches.

The brain circuits involved in compulsivity

Research suggests that compulsive behaviors involve certain circuits in the brain that connect areas of the frontal cortex to deeper brain structures called the striatum. These frontostriatal circuits help regulate our behavior.

In compulsive behaviors, there may be either too much activity in parts of the striatum or not enough control from the frontal cortex over the striatum. The chemical messenger glutamate seems to play an important role in how the frontal cortex regulates the striatum.

Memantine as a potential treatment

Memantine is a medication that affects how glutamate works in the brain. It’s currently used to treat symptoms of Alzheimer’s disease. Some initial studies have suggested memantine may help reduce OCD symptoms in adults when added to their usual treatment.

Since compulsive behaviors often start in childhood or adolescence, researchers want to know if memantine could potentially help younger individuals. However, we need to understand how memantine affects the developing brain and whether it can actually reduce compulsive behaviors at this age.

Using rats to study compulsive behaviors

To investigate this, the researchers used adolescent rats as a model to study compulsive behaviors. They gave some of the rats repeated injections of a drug called quinpirole, which causes the rats to develop compulsive checking behaviors. This means the rats repeatedly return to check certain locations, similar to compulsive checking seen in some humans with OCD.

The researchers then tested whether giving these rats memantine for 7 days would reduce their compulsive checking behaviors. They also used advanced brain imaging techniques to see if memantine changed the structure or function of the frontostriatal circuits in the rats’ brains.

What the study found

Memantine did not reduce compulsive behaviors

The main finding was that memantine treatment did not reduce the compulsive checking behaviors in the adolescent rats. The rats continued to show the same levels of compulsive checking after receiving memantine for a week.

No changes in brain connectivity

The brain scans also showed that memantine did not change the structural or functional connectivity in the frontostriatal circuits of the rats’ brains. This means the physical connections and communication patterns between brain regions remained the same after memantine treatment.

Different brain activation patterns

In a separate experiment, the researchers gave rats a single dose of memantine and immediately measured brain activity. In normal rats, memantine activated areas of the frontal cortex. However, in rats that had received quinpirole to induce compulsive behaviors, memantine did not activate the frontal cortex.

Interestingly, even in rats that only received a single dose of quinpirole, memantine did not activate the frontal cortex. This suggests that quinpirole somehow blocked or changed how memantine affects the brain.

Why didn’t memantine work in this study?

The researchers propose a few possible reasons why memantine did not reduce compulsive behaviors in this rat model:

1. Interactions between quinpirole and memantine: Both of these drugs affect dopamine systems in the brain. Quinpirole may have changed how memantine works, preventing it from having its usual effects.

2. Differences between rats and humans: The way compulsive behaviors develop in this rat model may be different from how they develop in humans. Memantine might still potentially help humans even though it didn’t help in this specific rat model.

3. Dosing and timing: The dose of memantine or how long it was given may not have been optimal. Different dosing regimens might potentially show different effects.

4. Age differences: This study used adolescent rats. The effects of memantine might be different in adult animals or humans.

Limitations of the study

It’s important to note some limitations of this research:

• The study used only male rats. The effects might be different in females.
• The rats were under anesthesia for some of the brain scans, which could affect the results.
• The compulsive behaviors were artificially induced by quinpirole. This may not perfectly mimic how compulsive behaviors develop naturally in humans.

What this means for treating compulsive behaviors

This study does not support using memantine to treat compulsive behaviors that develop during adolescence. However, it also doesn’t rule out that memantine might be helpful in some situations.

The findings highlight the complex interactions between different brain systems involved in compulsive behaviors. The interplay between glutamate (affected by memantine) and dopamine (affected by quinpirole) seems to be important.

More research is needed to understand:

• How memantine affects the brain in humans with compulsive behaviors
• Whether memantine might be helpful for some individuals even if it doesn’t work for everyone
• If different dosing strategies or combining memantine with other treatments might be effective

Conclusions

• Memantine treatment did not reduce compulsive checking behaviors in adolescent rats
• Memantine also did not change brain connectivity in circuits associated with compulsive behaviors
• The drug used to induce compulsive behaviors in the rats may have interfered with how memantine affects the brain
• This study doesn’t support using memantine for adolescent compulsive behaviors, but more research in humans is needed
• Understanding the complex brain systems involved in compulsivity may lead to better treatments in the future

While this study didn’t show promising results for memantine, it provides valuable information to guide future research. Developing new treatments for compulsive behaviors remains an important goal, especially for young people struggling with these challenging symptoms.