Cromwell BGSU 2021

Howard Casey Cromwell has been studying addictive behavior for nearly 20 years at Bowling Green State University.

A Bowling Green State University researcher is aiming to combat addiction using a new approach.

Howard Casey Cromwell, an associate professor, has been studying addictive behavior for nearly 20 years on campus.

“I’m interested in how animals change their motivation for one particular outcome and how that’s changed relative to all the different things that are orbiting around that,” Cromwell said.

His current research focuses on how alcohol-preferring rats — specifically bred to prefer alcohol — show inabilities to regulate intake of sucrose.

“The data is still somewhat preliminary, but the findings look pretty good in terms of showing that alcohol-preferring rats have alteration in their intake for sucrose. They also drank significantly more sucrose solution compared to the control,” Cromwell said.

How individuals shift their motivation when rewards change value is intimately connected to drug and alcohol addiction, especially during the pandemic. In March 2020, every American had many of their typical rewards change value or disappear altogether.

“One of the findings that we explored is how well the alcohol-preferring rats alter their behavior when sucrose levels shifted,” Cromwell said. “We shifted these fairly rapidly so that the animals were exposed to a high level of sucrose. Then a lower and then back to a high and lower and higher. Back and forth.”

Cromwell found that the controls, which were non-alcohol-preferring rats, change their preference for the sucrose solution based upon how concentrated it was. Sweet solution elicited huge consumption, while lower concentrations elicited lower consumption.

“The alcohol-preferring rats showed increased consumption and they were not showing these flip-flopping states of decrease and increase of consumption,” Cromwell said. “Instead, they were showing a sort of an on, or off all the time. Significant consumption and significant motivation for the sucrose reward started regardless of a shift in reward value.”

Hunger is a type of motivation state that requires increasing and decreasing the value of stimulus to achieve the end goal of satiety. Food restricting control animals led to increased sucrose consumption, whereas this was not the case with the alcohol-preferring rats.

“Alcohol-preferring rats, when they’re food restricted, don’t show a shift in their sucrose consumption. So, there’s this consumption at a high level, regardless of the food restriction state, and they also didn’t show this shift over to being sensitive to upshifts and downshifts of sucrose concentration,” Cromwell said.

Cromwell is excited about this promising research avenue, but said that this is preliminary data, not yet published.

“Next steps would be what happens when we give ethanol to these animals? Would they show a similar deficit? Or would they transition over to actually starting to become more sensitive to reward value?”

Cromwell believes looking at how valuable drugs are relative to other stimuli, and that this is absolutely necessary to understand addiction.

Cromwell believes a shift in the way of thinking is required for solving drug and alcohol-related deaths.

“The brain disease model of addiction has been around for 30 or 40 years. It hasn’t really led to a significant impact on the numbers of people that get addicted. So the one thing that’s clear from our work with fruit flies or rats is we need some paradigm shifts,” Cromwell said.

Addiction research is stymied with many seemingly intractable problems. The question all addiction researchers seek to answer is why a human would choose to use a substance until they die. For addicts such as these, Cromwell said one has to wonder how valueless everything else has become, and how invaluable the high must be to make such a gamble day in and day out.

“We need new research,” Cromwell said.

Cromwell says clinical solutions to prevent morbidity of this kind are very far off for a couple of reasons.

“Alcohol acts on a GABA receptor,” Cromwell said.

This is the main inhibitory brain receptor in the body, and alcohol acts on these receptors, so directly intervening in the receptor to prevent intoxication-related deaths is fruitless, which isn’t the case with opioid receptors.

Recently, Narcan has been fielded by the medical community to prevent opioid overdose death, but the prospective for a similar medication for alcohol overdose is bleak.

“GABA receptors are just more intimately related to our everyday function in life than opioid receptors,” Cromwell said.

This means solutions focusing on why organisms can shift their value of alcohol so much may be the only hope for preventing alcohol-related morbidity. The next step in Cromwell’s research is to observe the way alcohol-preferring rats value alcohol when its absolute value changes.

“We’re not really sure what path to go, but possibly they’re going to show this increased intake of ethanol,” Cromwell said.