Brown University scientists conducting experiments with fruit flies found that hunger drives cravings for alcohol, providing context for understanding similar processes in the human brain.
PROVIDENCE, R.I. [Brown University] - Researchers at Brown University have discovered a molecular link between hunger and the formation of "reward" memories that play a role in alcohol addiction. The insight could inform strategies for treatment and prevention, the scientists say.
The study, led by researchers at Brown's Carney Institute for Brain Science, mapped and isolated hunger-responsive neurons in the brain of the common fruit fly, which has a sophisticated brain that makes it a useful model for observing neural behavior. The team found that hunger in food-deprived flies activated neurons containing octopamine - a fight-or-flight neurotransmitter equivalent to human norepinephrine - that influences whether alcohol is remembered as rewarding.
The findings, published in Current Biology, provide new context for understanding mechanisms that drive alcohol cravings and addiction.
"If we can understand at a smaller level how an organism like a fly can remember alcohol, that is a step forward to understanding how humans associate cues with alcohol and can provide hints at how we can prevent relapse and treat addiction," said Lewis Sherer, a postdoctoral researcher at Brown and a study first author.
Sherer works in the lab of Karla Kaun, an associate professor of neuroscience at Brown affiliated with the Carney Institute. Previous studies by scientists in Kaun's lab have helped to uncover the role of memory formation underlying addiction - how memories of alcohol as a reward can drive cravings - as well as the role alcohol and other addictive substances play in altering memory pathways.
Sherer said that prior studies have focused mainly on "reward" molecules such as dopamine. But researchers are also beginning to understand the implications of different internal states, such as hunger, thirst and pain, in the formation of reward memories that drive alcohol addiction. For this study, the team wanted to further investigate the potential role of octopamine, a fly version of norepinephrine that is activated by hunger, thirst and pain to influence fly behavior, memory and sensory processing.
The researchers observed that genetically silencing or activating a single octopamine neuron in the brain (VUMa3) influenced how soon flies found alcohol rewarding and affected alcohol preference only when the flies were hungry. According to Kaun, the takeaway is that hunger can recruit new neurons to communicate with brain circuits that associate cues in the environment with a rewarding feeling connected to alcohol.
"For example, perhaps you usually pass by a bar you like on your way home from work every day," Kaun said. "But maybe today you're hungry after skipping lunch. You're more likely to notice that cute sign and feel like stopping to have a drink. The cute sign, which didn't entice you when you weren't hungry, can trigger your craving for alcohol."
The researchers said the work could bring scientists one step closer to determining how external stressors, such as food insecurity, could influence the internal reward systems involved in alcohol and drug addiction.
"We can say from this study that the conditions a person goes through in their lives can influence how they respond to alcohol," Sherer said. "If a person grows up in conditions where they're very hungry or very stressed, they might have a higher propensity to develop an alcohol addiction."
Funding for the research was provided by the National Institute on Alcohol Abuse and Alcoholism ((R01 AA024434), the National Institute of Neurological Disorders and Stroke (F99 NS118741), the National Institute of General Medical Sciences (R01 GM115510), the National Institute on Aging ((T32 5T32AG041688), the National Institute on Deafness and Other Communication Disorders ((R01 DC017146 and R01 DC020703), the Hubert & Richard Hanlon Trust and Howard Hughes Medical Institute, as well as the Carney Institute.
