The interplay between a pair of neurotransmitters--acetylcholine and glutamate--may offer a new key to controlling nicotine addiction, according to a team of investigators from Rockefeller University.
The researchers already knew that the neurotransmitters played a big role in an area of the brain known as the habenula. Then they developed mouse models for the disease whose habenular neurons didn't make acetylcholine, which impaired the action of glutamate.
"In our experiments, we observed that the elimination of acetylcholine affected glutamate in this brain region in two ways," says Ines Ibanez-Tallon, a research professor in the Laboratory of Molecular Biology. "First, the amount of glutamate released by neurons was reduced. And second, the reuptake of glutamate back into vesicles was impaired. Both of these mechanisms affect the excitability of neurons, meaning normal signaling is disrupted."
And once they removed acetylcholine from the equation, investigators add, the mice didn't respond to the body's reward system spurred by nicotine, offering a potential new approach to managing nicotine addiction.
Much work remains on this target, though.
"Because most nerve cells that release acetylcholine also release glutamate at the same time, the next challenge is to investigate whether the synergy between these two neurotransmitters is important for other functions that involve acetylcholine, such as memory and cognition," says the researcher.