Washington State University researchers report that targeting a circuit from the prelimbic cortex to the paraventricular thalamus can reduce opioid relapse in a preclinical model. The paraventricular thalamus is known to process drug-associated cues and motivational states, and the team showed that signals from the prelimbic cortex strongly activate this area. The work comes from the integrative physiology and neuroscience department in the College of Veterinary Medicine and appears in the Journal of Neuroscience.
Using an animal model that mimics human opioid use, the group demonstrated that lowering activity in the pathway significantly lowered heroin-seeking behavior. The project was led by graduate researcher Allison Jensen under assistant professor Giuseppe Giannotti. The researchers emphasize that the same brain pathway exists in humans and that stopping cravings is a major challenge for people who quit. They also note the broader context: opioids were the leading cause of drug overdose deaths in the United States, with more than 79,000 deaths in 2023, and relapse is common after inpatient care.
Two methods were tested to reduce pathway activity. First, a chemogenetic method introduced a designer receptor into prelimbic cortex neurons that project to the paraventricular thalamus; activating that receptor with a specific drug reduced pathway activity and lowered heroin-seeking. Second, an optogenetic approach used a fiber-optic implanted in the paraventricular thalamus to deliver a low-frequency light pattern that gradually desensitized the connection; this light method nearly doubled the effect seen with chemogenetics. Giannotti suggested that a similar idea, such as deep brain stimulation, could potentially be adapted for humans and for other abused substances including cocaine, alcohol and nicotine. The lab's next step is to study how environmental cues, like lights and sounds linked to drug use, dynamically activate this circuit to drive relapse.
Difficult words
- circuit — group of connected neurons or neural connections
- prelimbic cortex — front brain area involved in decision and control
- paraventricular thalamus — thalamic region that processes motivation and cues
- pathway — route of connected neurons between brain areas
- relapse — return to drug use after a period of abstinence
- chemogenetic — method using engineered receptors activated by drugs
- optogenetic — technique using light to control genetically modified cells
- desensitize — make a connection less responsive to stimulationdesensitized
- craving — strong desire to use a drug or substancecravings
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Discussion questions
- What advantages and risks might there be in adapting deep brain stimulation for treating opioid relapse?
- How could environmental cues like lights and sounds trigger relapse, based on the article?
- What challenges do researchers face when applying results from animal models to human patients?
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