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June 1, 2022 – “We’re trying to provide a better understanding of the neurotransmission side of the compulsions that define addiction, to understand which neurons are relevant on the network level,” Kroener said.

He said changes in an addicted person’s brain persist beyond the initial withdrawal period.

“These persistent neuroadaptations increase alcohol’s incentive salience — the motivation to seek rewards through alcohol,” he said. “The desire to seek out the addictive substance escalates as someone tries to quit.”

With the new funding, Kroener will focus on changes in the medial prefrontal cortex and deficits in cognitive function associated with alcohol use.

“These deficits fuel compulsion and relapse into alcohol consumption,” he said. “We hope to find the specific synaptic mechanisms that yield these changes in the brain as it transitions from controlled alcohol-seeking to a compulsive behavior.” Experiments in the study will be conducted on mice and will use a technique called optogenetics, which uses light to selectively impede the activity of neurons.

“We can select neurons to ‘trap’ during the drug-taking behavior,” Kroener said. “Then, by activating or inhibiting the activity of those cells, we can see whether that influences the animals’ behavior.”

The experiment relies on a test concept, modified for rodents, derived from the Wisconsin Card Sorting Test, which has been used for more than half a century to measure frontal lobe dysfunction.

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