How Does Dopamine in the Striatum Affect Brain Activity and Behavior?

What you need to know

• Researchers activated dopamine neurons projecting to a part of the striatum in rats’ brains
• This increased exploratory behaviors and reduced anxiety-like and compulsive-like behaviors in the rats
• It also decreased brain activity in the frontal cortex but increased glutamate levels there
• The findings provide insight into how striatal dopamine affects brain function and behaviors related to conditions like OCD

The striatum and dopamine

The striatum is a region deep in the brain that plays important roles in movement, motivation, and decision-making. It receives signals from many other brain areas and helps coordinate behavior. The striatum is part of a larger circuit in the brain that includes the cortex (the outer layer of the brain) and other deep brain structures.

Dopamine is a chemical messenger in the brain that is important for reward, motivation, and movement. Many dopamine neurons project to the striatum and release dopamine there. Changes in striatal dopamine signaling have been linked to various neuropsychiatric conditions, including obsessive-compulsive disorder (OCD) and schizophrenia.

However, it has been unclear whether changes in striatal dopamine are a cause or a consequence of dysfunction in other parts of the brain circuit in these conditions. This study aimed to specifically activate dopamine signaling in one part of the striatum in rats and see how it affected brain activity and behavior.

Activating dopamine neurons

The researchers used a technique called chemogenetics to selectively activate dopamine neurons that project to the medial dorsal striatum in rats. This allowed them to increase dopamine signaling specifically in this part of the striatum.

They then conducted several experiments to assess how this activation affected the rats’ behavior and brain activity:

Changes in behavior

After activating the dopamine neurons, the researchers observed that the rats:

• Moved around more and explored their environment more
• Spent more time in the center of an open field (suggesting reduced anxiety)
• Reared up on their hind legs more often (an exploratory behavior)
• Spent less time grooming themselves (a behavior that can become compulsive)

These behavioral changes suggest that increasing dopamine in this part of the striatum made the rats less anxious and reduced compulsive-like behaviors.

Changes in sensory processing

The researchers also tested how the rats responded to startling noises. They found that female rats (but not males) showed an improved ability to reduce their startle response when given a warning sound first. This process, called prepulse inhibition, is often impaired in conditions like OCD and schizophrenia. The improvement seen here suggests activating striatal dopamine neurons may help normalize this type of sensory processing in some cases.

Changes in brain activity

To look at how brain activity was affected, the researchers used PET imaging to measure glucose metabolism (an indicator of brain activity) throughout the rats’ brains. They found that activating the dopamine neurons led to:

• Decreased activity in parts of the frontal cortex
• Increased activity in the cerebellum

This pattern of decreased frontal cortex activity is the opposite of what is often seen in brain scans of people with OCD.

Changes in brain chemistry

The researchers also used magnetic resonance spectroscopy to measure levels of certain chemicals in the rats’ brains. They found:

• Increased levels of glutamate (the brain’s main excitatory chemical messenger) in the frontal cortex and striatum
• Increased levels of N-acetylaspartylglutamic acid (NAAG) in the frontal cortex

Interestingly, people with OCD often show decreased glutamate levels in the frontal cortex. So again, activating striatal dopamine neurons seemed to produce the opposite effect of what is seen in OCD.

Conclusions

• Activating dopamine neurons that project to part of the striatum reduces anxiety-like and compulsive-like behaviors in rats
• This activation also decreases frontal cortex activity while increasing glutamate levels there
• The effects on brain activity and chemistry are opposite to patterns often seen in OCD
• These findings help clarify how striatal dopamine affects the larger brain circuit and may point to new treatment targets for conditions involving this circuit

This study provides important insight into how dopamine signaling in one part of the striatum can influence activity throughout a larger brain circuit and affect behavior. The findings suggest that increasing striatal dopamine may help reduce anxiety and compulsive behaviors in some cases.

However, it’s important to note that this study was done in rats, and the effects may be different in humans. Additionally, the chemogenetic technique used to activate neurons is not currently possible in humans. Nonetheless, understanding these brain circuits better may help researchers develop new treatments for conditions like OCD that involve dysfunction in these circuits.