Reelin: A Marker and Regulator of Cocaine-Activated Neurons in the Brain's Reward System

Recent research has shed light on how cocaine affects brain neurons, particularly within the nucleus accumbens, a critical brain region involved in motivation and addiction. Studies show that only about 10% to 20% of neurons in this area are activated by cocaine, yet these neurons play a significant role in driving drug-related behaviors.

A groundbreaking study published in Science Advances by scientists from the University of Alabama at Birmingham identifies a glycoprotein called reelin as a marker for those neurons activated by cocaine. Using advanced genetic tools, researchers reduced reelin expression in rat models to investigate its role in neuronal function and behavior.

The results demonstrated that decreasing reelin levels diminished gene expression associated with cocaine activity, altered neuron excitability, and impaired neural responses. Behaviorally, rats with suppressed reelin expression showed reduced movement, less place preference for cocaine, and decreased self-administration of the drug, highlighting reelin's essential role in cocaine's effects.

Further analyses revealed that reelin is highly expressed in medium spiny neurons, the main neuronal cell type in the nucleus accumbens that contains dopamine receptors. Interestingly, over 80% of cocaine-activated medium spiny neurons expressed reelin mRNA, indicating a substantial association.

The study leveraged single-nucleus RNA sequencing data, uncovering that reelin's expression enables neurons to be more excitable and responsive to cocaine. Historically known for its role in brain development and synaptic plasticity, reelin’s involvement in drug-induced neural adaptations was unexpected but significant.

Overall, these findings position reelin as a crucial molecular marker and potential therapeutic target for cocaine addiction. Manipulating reelin signaling could pave the way for precise interventions in reward circuitry, helping to treat cocaine use disorder.

For more details, see the full study by Brida et al., published in Science Advances (2025).