Drug addiction is often thought of as neuron–centric, but in a study published in the Proceedings of the National Academy of Sciences journal, MD/PhD student Daniel Kashima and his mentor, Brad Grueter, PhD, show that the immune system also plays a critical role.

They studied the consequence of lacking toll–like receptor 4 (TLR4) on drug–associated physiology and behavior. TLR4 is a pattern–recognition molecule of the innate immune system.

They found that TLR4 knockout mice exhibited a difference in the ability to dynamically change the strength of neuronal connections in the nucleus accumbens core (NAc), a key brain area that processes motivation and reward.

This was associated with a deficit in drug–reward learning. They further showed that microglia, one of the brain’s immune cells, are the primary cell type that expressed TLR4.

These results suggest that TLR4 is a novel regulator of NAc neuronal physiology and associated drug–reward learning.