Summary:
Supported by a five-year K01 award of more than $943,000 from the National Institute on Drug Abuse (NIDA), neuroscientists at the University of Central Florida are investigating how nicotine reshapes neuronal mitochondria in the nucleus accumbens. By examining subcellular changes that promote drug-seeking behavior, the team aims to reveal molecular targets for better treatments for nicotine use disorder and related addictions.
Key Facts:
- Focus on the Brain’s Reward Center: The research targets the nucleus accumbens, a forebrain hub that integrates reward-related signals to influence learning, decision-making, and compulsive behavior.
- Mitochondria as Signaling Hubs: Beyond supplying energy, mitochondria are studied here for their roles in controlling neuronal communication, gene expression, and steroid production during drug exposure.
- Rising Use of Nicotine Pouches: The project responds to a changing nicotine landscape: survey data show the use of oral nicotine pouches among U.S. youth and young adults nearly quadrupled between 2022 and 2025.
Source: University of Central Florida (UCF)
Background: While traditional cigarette smoking has declined, new nicotine delivery products—especially electronic cigarettes and oral nicotine pouches—have become widespread. These novel formats change how nicotine is used and who is affected, making it vital to understand how the brain responds at a cellular and molecular level.
Decades of behavioral research have advanced our knowledge of addiction, but effective, broadly applicable therapies for nicotine use disorder remain limited. Existing treatments help some people but often have side effects or fail to produce lasting abstinence. To identify more precise, potentially safer interventions, researchers are turning to the cell biology that underlies addictive behavior.
Assistant Professor Dr. Cali Calarco, at UCF’s Burnett School of Biomedical Sciences, leads the lab conducting this work. Her team uses modern neuroscience tools to examine how prolonged nicotine exposure alters the internal structure and function of neurons in the nucleus accumbens. The project is funded by a five-year, $943,000-plus K01 grant from NIDA.
“We want to understand what’s really influencing the neuron,” Dr. Calarco said. “Which component is critical for the neuron function that leads to drug-seeking behavior?”
The Nucleus Accumbens and Mitochondrial Dynamics
The nucleus accumbens sits at the center of the brain’s reward circuit and plays a pivotal role in reinforcement learning, incentive salience, and behavioral choice. Dr. Calarco describes it as a compact “computer” that integrates signals from across the brain to guide actions related to reward.
Rather than treating that region as uniform, the research dissects how different neuron subtypes in the nucleus accumbens respond to nicotine. A central focus is the mitochondrion—traditionally portrayed as the cell’s power plant but increasingly recognized as a critical regulator of neuronal function.
In addition to meeting high energy demands, mitochondria influence synaptic communication, calcium signaling, gene transcription, and the synthesis of steroid hormones. These functions make mitochondria well positioned to shape the plasticity that underlies habit formation and compulsive drug-seeking.
“Mitochondria have been underappreciated in neurons previously,” Calarco noted. “Neurons are incredibly complex and carry out demanding electrical and chemical tasks that require a lot of energy. But mitochondria also influence how neurons talk to each other, regulate gene transcription and translation, and affect hormone production.”
From Cellular Bioenergetics to Targeted Therapies
Building on prior postdoctoral studies at the University of Maryland, Baltimore—where she examined mitochondrial changes linked to cocaine-seeking—Calarco’s lab now monitors how nicotine alters mitochondrial shape, intracellular movement, and metabolic signaling in real time. These experiments combine molecular biology, imaging, and behavioral models to connect cellular changes with observable drug-seeking behaviors.
By identifying which mitochondrial and signaling pathways are disrupted by chronic nicotine exposure, the researchers hope to pinpoint targets for therapies that act directly on affected neural circuits. Such targeted approaches could reduce the broad systemic effects and side effects associated with many current treatments.
“There aren’t that many substance use disorder treatments, and the ones available only work for a subset of people,” Calarco said. “There is room for improvement in nicotine use disorder therapies, and new pathway targets may provide more effective treatments with fewer side effects.”
Because the nucleus accumbens relies on conserved molecular mechanisms for reward learning, insights into mitochondrial contributions could extend beyond nicotine. Understanding these subcellular drivers may inform interventions for other substance use disorders and for compulsive behaviors that share overlapping circuitry.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The associated journal paper will be reviewed in full upon release.
- Additional context was provided by our staff.
About this Addiction Research:
- Media Contact: Eric Eraso
- Source: UCF
- Image Credit: Image credited to Neuroscience News