CASPER, Wyo. — Sugar and cocaine may have “largely distinct” effects on a part of the brain that plays “a central role in the risk-reward circuit.”
This difference is suggested by research into the effects of cocaine and sucrose on the “nucleus accumbens,” a portion of the brain important to these risk-reward circuits, the University of Wyoming said on Wednesday, Oct. 28.
UW School of Pharmacy Assistant Professor Ana Clara Bobadilla is the lead author of a paper titled “Cocaine and Sucrose Rewards Recruit Different Seeking Ensembles in the Nucleus Accumbens Core” that explores the findings of research which involved genetically modified mice, according to UW’s release. Bobadilla is also an assistant professor in the WWAMI (Washington, Wyoming, Alaska, Montana and Idaho) Medical Education Program.
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The risk-reward circuit in the brain largely relies on three types of neurotransmitters, according to UW:
- dopamine: a neurotransmitter “which promotes desire”
- serotonin: “whose effects include satiety and inhibition”
- glutamate: “which drives goal-directed behaviors and responses to reward-associated cues and contexts”
The finding that cocaine and sucrose have largely distinct effects on the nucleus accumbens points to “the possibility that drug use can be addressed without affecting biologically adaptive seeking of reward,” UW says.
“We established that, in the nucleus accumbens, a key brain region of reward processing, the neuronal ensembles — a sparse network of neurons activated simultaneously — are reward-specific, and sucrose and cocaine ensembles are mostly nonoverlapping,” Bobadilla said in the release.
Bobadilla told UW that the way in which each “reward-specific ensemble” recruits the nucleus accumbens is uknown.
“However, using molecular biology tools, Bobadilla was able to identify what type of cells was recruited in both the cocaine and sucrose ensemble,” the release states. “These cells are known as GABAergic projection neurons, also called medium spiny neurons. They comprise 90 percent to 95 percent of the neuronal population with the nucleus accumbens. These medium spiny neurons express the dopamine D1 or D2 receptor.”
The research found that sucrose and cocaine mainly recruit D1 receptors “expressing medium spiny neurons.” Bobadilla told UW that this finding falls in line with “the general understanding in the field that activation of the D1 pathway promotes reward seeking, while D2 pathway activation can lead to aversion or reduced seeking.”
“In humans, drugs are rarely used in the vacuum,” she said. “Most of us have complex lives including lots of sources of nondrug rewards, such as food, water, social interaction or sex.”
“Like drugs, these rewards drive and influence our behavior constantly. The dual cocaine and sucrose model used in this study allows us to characterize the cocaine-specific ensemble after the mice experienced sucrose, another type of competing reward. It is a more complex model, but one that is closer to what occurs in people suffering from substance use disorders, who fight competing rewards daily.”
UW says that Bobadilla’s focus is now on how cells are recruited in neuronal ensembles and “she aims to address another fundamental question in addiction research: whether the same network-specific mechanisms underlie the seeking of all drug rewards.”
“All drugs of abuse share high probability of relapse,” Bobadilla told UW. “However, each class of addictive drug displays different acute pharmacology and synaptic plasticity. We are now investigating if reward-specific properties of ensembles can explain these differences.”
Babadilla’s research for the project was conducted while she was completing postdoctoral work as the Medical University of South Carolina, UW says. The research began in 2017.
“The study was funded, in part, by Bobadilla’s postdoctoral mentor, Peter Kalivas, a professor and chair of neuroscience at the Medical University of South Carolina, and by a National Institutes of Health Pathway to Independence Award Bobadilla obtained in early 2019,” UW says.
The research paper was published in the Sept. 28 issue of Molecular Psychiatry.
“The journal publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment,” UW says. “The emphasis is on studies at the interface of pre-clinical and clinical research, including studies at the cellular, molecular, integrative, clinical, imaging and psychopharmacology levels.”