Brain Circuit That Works to Control Impulsivity Identified in Rats, Study Suggests

A particular signaling protein in the brain, called melanin-concentrating hormone (MCH), was seen to help regulate impulse control in rats, a study reports.

This finding may have implications for disorders where impulse behaviors manifest, from binge eating and drug addiction to Parkinson’s disease.

The study, “Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone,” was published in Nature Communications.

Impulsive behaviors are those done without thought to the long-term consequences. Such behaviors play obvious roles in diseases like addiction, and they often become dysregulated in conditions like Parkinson’s.

“We discovered the brain connections that keep impulsivity in check,” Scott Kanoski, MS, PhD, a study co-author and a professor at the University of Southern California, said in a press release. “The key to this system is a neuropeptide that we’ve been focusing on, melanin-concentrating hormone, in studies on appetite and eating.”

Researchers trained rats to press a lever in order to get a treat — a high-sugar, high-fat delicacy that Kanoski compared to a “little donut hole.” But there was a catch: the rats wouldn’t get the treat until 20 seconds after they had pressed the lever, and every time they pressed the lever, the countdown restarted.

This works as a test for impulsivity because more impulsive rats would be expected to hit the lever more frequently — even though it meant getting fewer treats in the end.

Melanin-concentrating hormone (MCH) is signaled by brain cells in the hypothalamus, an area of the brain that produces hormones which control several functions, such as body temperature, sex drive, and hunger.

The researchers found that, when they increased MCH signaling in the rats’ brains (via a variety of techniques, including injecting MCH and using viruses to genetically modify MCH-producing neurons), the rats hit the levers more frequently — again, indicating increased impulsivity.

Researchers then gave the rats a choice between two levers: one with the same 20-second delay per one treat, the other with a longer delay (30 to 45 seconds) that gave five treats. The rats with increased MCH signaling pressed the 20-second delay levers more often, suggesting an increase in delay discounting — that is, they wanted the reward sooner, even if waiting would mean a larger overall reward. Again, this is indicative of high impulsivity levels.

These experiments suggested that other behaviors could also be affected. For instance, the team wondered if increased MCH signaling made the rats more hungry for these particular treats. But when the researchers gave the rats free access to treats, they ate the same amount regardless of whether they had increased MCH signaling or not, discrediting this idea.

It is also conceivable that MCH helped regulate the rats’ internal clocks, making it harder for them to keep track of how long it had been since they last pressed the lever. But again, experiments that examined the rats’ ability to do other time-related tasks showed no differences.

Rats with increased MCH signaling also didn’t exhibit any difference in the frequency with which they hit levers that weren’t linked to a reward, suggesting that the observed difference in behavior wasn’t due to general hyperactivity.

By ruling out these other possible explanations, the researchers concluded that the change in behavior was specifically due to differences in impulse control.

These scientists then went the other way, decreasing MCH signaling using a technique called RNA interference, which ultimately blocks gene expression: the process by which information in a gene is synthesized to create a working product, like a protein.

They expected that this would have the opposite effect. But, interestingly, rats with lesser MCH signaling also hit the levers more frequently in the original task — these rats were more impulsive, too.

Additional tests and brain imaging scans suggested that most MCH signaling starts in a brain region called the ventral hypothalamus and ends up in the nucleus accumbens, both of which are associated with hunger and reward responses. The precise circuitry is still being worked out and will require future studies to fully understand.

“Surprisingly, our results [in the above experiment] showed that animals behaved more impulsively when MCHR1 [MCH receptor 1] levels were knocked down in the vHP [ventral hypothalamus], indicating an increase of impulsivity when vHP MCHR1 tone is perturbed in either direction,” the researchers wrote.

And, they added, “our results show that MCH signaling in the vHP increases impulsive responding and impulsive choice for a palatable food reinforcer but has no effect on food-motivated responding, locomotor activity, or clock speed timing. We conclude that the projection pathway from MCH neurons … to the vHP plays a role in mediating impulsivity.”

Emily Noble, MS, PhD, a professor at the University of Georgia and study co-author, noted that fully understanding how this signaling works may pave the way for future therapies for impulsivity-related diseases.

“We are not quite in a place where we can target therapeutics to specific brain regions yet,” Noble said, “but I think that day will come.”