Researchers in the lab of Dr. Brian Baldo observed changes in behavior after rats were treated in the prefrontal cortex – the brain’s site for planning and self-control. Rats infused with naturally occurring opioid compounds that act like opiate drugs exhibited greatly exaggerated food motivation and impulsive food-seeking behaviors.
The neuroscientists also showed that blocking parts of the circuit that connect the prefrontal cortex to downstream, more ‘primitive’ eating-control structures, ended the pathological food responses caused by prefrontal opioid stimulation.
These findings led Baldo, to propose the prefrontal cortex as a previously unappreciated yet highly-sensitive “hot spot” for opioid actions. Targeting this region could lead to new treatments for out-of-control food-seeking (and possibly drug-seeking) behavior.
The opinion article, appearing in the June issue of the journal Trends in Neurosciences, describes a novel theory regarding the brain mechanisms and specific brain circuits underlying excessive binge behavior.
Baldo, assistant professor of psychiatry in the University of Wisconsin School of Medicine and Public Health, writes that, under certain conditions, opioid peptides act in the prefrontal cortex to drive impulsive reward-seeking behavior.
Normally, opioid actions in the prefrontal cortex are balanced by a neural circuit that maintains reward function within healthy limits (a “limiter” circuit). Opioid transmission in the prefrontal cortex also engages a motivational “driver” circuit, which causes excessive reward-driven behavior. If the system is functioning properly, Baldo says, the two systems balance each other out to produce a normal degree of motivated behavior.
“What we saw is that dysfunction somewhere in the circuit led to excessive reward-seeking behavior and food impulsivity. These are crucial features of binge eating,” Baldo says.
Scientists in Baldo’s lab infused rats with µ-opioids, a type most closely mimicking heroin’s effects. These rats became hyperactive and over-ate sugary food. They also showed that blocking opioid receptors in the prefrontal cortex was sufficient to “erase” the naturally occurring food impulsivity caused by hunger.
Further research identified two pathways emanating from the prefrontal cortex, and targeting distinct sub-cortical brain regions, that appear to mediate the “limiter” and “driver” actions described above. Finally, the lab gathered evidence that allowing rats to repeatedly gorge themselves on sugary, fatty food eventually weakened the function of the “limiter circuit.”
Baldo says that while the prefrontal cortex has long been considered important in understanding or treating addictive behavior, the neurochemicals that act within this brain structure are not fully understood. Opioids appear to be a powerful yet under-appreciated ‘player’ in the neurochemical milieu that governs prefrontal function.
“We believe the prefrontal cortex, which is the brain’s self-control and decision-making center, could be a sensitive “hot spot” for opioid actions,” Baldo says. “Because this theory specifies the neurochemical transmitters involved at each step of the prefrontal cortical circuit, it suggests a research model for testing psychiatric medications, or combinations of medications, to treat out-of-control binge behavior.
Baldo recently received a major grant from the National Institute for Mental Health to further refine the model, and to explore the possibility of innovative poly-drug approaches that simultaneously target the prefrontal cortex along with downstream brain structures—hopefully providing new directions for a set of notoriously difficult-to-treat psychiatric illnesses.
Susan Lampert Smith