December 1, 2017

The road to addiction recovery might become a little less rocky, thanks to a recent study by researchers at the Yerkes National Primate Research Center. Researchers suggest the drug fasudil, approved in Japan for cerebral vasospasm and stroke, could be an effective tool for treating drug abuse and preventing relapse.

Most of our everyday actions come from habits, not from deliberate decision-making. This can be detrimental in the case of drug abuse and drug-seeking behavior, says lead author Shannon Gourley, assistant professor of pediatrics, psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center.

“Some habits are adaptive – for example, turning off a light when you exit a room – but others can be maladaptive, for example in the case of habitual drug use. We wanted to try to figure out a way to help ‘break’ habits, particularly those related to the highly addictive drug cocaine,” says Gourley.

She and former graduate students Andrew Swanson and Lauren Depoy first tested fasudil in situations where they had trained mice to poke their noses in two chambers, based on rewards of both food and cocaine. Then, the researchers changed the rules of the game – mice could now only get a reward from one chamber, instead of both. Fasudil helped the mice adjust and display “goal-directed” behavior, rather than their previous habit-based behavior.

Next, the researchers trained the mice to supply themselves a sweet cocaine solution. After the mice formed habit-based behavior, researchers changed the nature of that experience: the cocaine was paired with lithium chloride, making the mice feel sick. Fasudil treatment nudged the mice to give themselves less cocaine afterward, rather than continuing to respond habitually. Fasudil didn’t make cocaine itself less pleasurable, but was specifically modifying the habit process.

Unlearning habits involves remodeling connections made by cells in the brain. Fasudil seems to promote the pruning of dendritic spines, structures that help neurons communicate, by inhibiting Rho kinase, which helps stabilize cells’ internal skeletons. The drug thereby loosens the cell structures and appears to reduce the density of dendritic spines in the region of the brain important for learning new behaviors. Importantly, tests show fasudil must be directly paired with new learning to have that effect.

While overactive synaptic pruning has been proposed to play roles in Alzheimer’s disease and schizophrenia, when used appropriately, fasudil and similar compounds are promising candidates for drug addiction therapy.

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