Research has shown that neuronal PAS domain protein 4 (NPAS4) is a key factor in the formation and maintenance of drug-context associations.

New Delhi: Cocaine is notorious for its overdose deaths and unpredictable behavior, affecting figures ranging from rock legend Tom Petty to Charlie Sheen, formerly the highest-paid star on television. It has long destroyed both talent and wealth.

Scientists have now uncovered specific components of cocaine that fuel its reputation as a dreaded narcotic.

Researchers at the Medical University of South Carolina have discovered how cocaine activates a specific protein in the brain, which then controls normal brain circuits, leading to increased drug-taking activity. The finding, published in Nature Communications, sheds light on the processes underlying drug-context associations, which are important in relapse risk.

The research, directed by Christopher Cowan, chair of the Department of Neuroscience at MUSC, points to neuronal PAS domain protein 4 (NPAS4) as a key factor in the formation and maintenance of these drug-context associations.

“These drug-context associations become future triggers for drug discovery,” explained Cowan, emphasizing the importance of understanding how these associations are formed.

The team at MUSC focused on a select group of cells in the nucleus accumbens, an area of ​​the brain important for controlling motivation and learning related to rewards. Their findings showed an increase in neurons expressing NPAS4 after cocaine exposure. NPAS4, a transcription factor, orchestrates cellular responses to neuronal activity, including various stimuli, drugs.

Interestingly, research has indicated that NPAS4 in neurons expressing D2 dopamine receptors, as opposed to D1 receptors, plays a critical role in context-associated drug-seeking behavior.

D2 neurons normally act as a brake on drug-taking behavior. However, NPAS4 appears to moderate this inhibitory effect, thereby strengthening drug-reference associations and increasing relapse risk.

“The drugs are probably doing several things,” Cowan said, “not only are they strengthening and creating contextual memories, but they're also suppressing the brain's ability to resist this association.”

Understanding how NPAS4 mediates these effects would be an important advance, potentially leading to new therapeutic targets aimed at reducing the risk of relapse.

(with IANS input)