Novel Anti-craving Mechanism Discovered to Tackle Cocaine Relapse

Cocaine persists to be one of the most commonly abused illegal drugs in the United States. A novel anti-craving mechanism can help to reduce cocaine craving-induced relapse, according to a new study. The findings are published in the journal Molecular Psychiatry.

Pre-clinical literature advises that targeting glucagon-like peptide-1 receptors (GLP-1Rs) in the brain may outline a novel approach to treating cocaine usage disorder. Specifically, GLP-1R agonists, which are FDA-approved for treating diabetes and obesity, have been shown to decrease voluntary drug taking and seeking in pre-clinical models of cocaine used disorder.

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However, the same neural circuits and cell types that mediate the suppressive effects of GLP-1R agonists on cocaine-seeking behavior are mostly unknown.

A new research team from the University of Pennsylvania School of Nursing (Penn Nursing) has discovered that GLP-1Rs are expressed on specific cell types and neural circuits in the brain that reduce cocaine-seeking behavior. Researchers have also found that GLP-1Rs are displayed primarily on GABAergic neurons in the hindbrain.

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The effectiveness of the GLP-1R agonist exendin-4 to reduce cocaine-seeking depends, in part, on the activation of these GABA circuits. Moreover, activating these endogenous anti-craving circuits in the brain using viral-mediated gene delivery methods was sufficient to reduce cocaine-seeking behavior.

These findings highlight GLP-1R-expressing anti-craving circuits in the brain that could work as potential targets to overcome cocaine craving-induced relapse.

Lead investigator Heath D. Schmidt, Ph.D., Associate Professor of Nursing at Penn Nursing, said, "Overall, the translational implications of these results are profound in that they support GLP-1R-focused therapeutic strategies for the treatment of cocaine craving and relapse."

Source: Medindia