Novel Neurotransmission Influences Drug Addiction

For many years, scientists have been mostly unsuccessfully in finding a molecular therapy for drug addiction. However, a team of researchers from the University of Iowa (UI) has now discovered a novel neurotransmission that influences addiction-related memory.

The research, which was published June 22, 2014, in Nature Neuroscience, highlighted the behavior of proteins called acid-sensing ion channels (ASICs) that have been attributed to learning and memory in previous research, and are also significantly present in brain compartments associated with drug addiction, according to a statement.

“Because ASIC has been suggested to promote associative learning, we hypothesized that disrupting ASIC in the nucleus accumbens (NAc) would reduce drug-associated learning and memory,” the authors wrote.

For their study, the investigators rewarded mice that moved to a particular location in their chambers with cocaine. In one group of mice, the researchers decreased ASIC activity in the NAc, where addiction-based memory is stored. In doing so, the investigators discovered that “disrupting ASIC in the mouse NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC in addiction-related behavior.”

"Always before, the data suggested that when you get rid of ASICs, learning and memory are impaired," John Wemmie, Professor of Psychiatry in the UI Carver College of Medicine, commented. "So, we expected the same trend when we studied reward-related learning and behavior, and we were surprised to find the opposite."

For their second experiment, the researchers trained the mice to hit a lever that allowed them to self-administer cocaine. When the investigators decreased ASIC activity in the NAc, they found the mice self-administered cocaine more often. Conversely, increasing the channels resulted in less cocaine administration.

Based on their observations, the researchers reported finding “a previously unknown postsynaptic current during neurotransmission that was mediated by (ASICs), and thus well positioned to regulate synapse structure and function.”

“Together, these data suggest that ASIC inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission,” the authors penned.

In the future, Wemmie and his colleagues plan to determine whether the behavior is similar in other types of addiction.

"There are many forms of addiction," Wemmie commented. "We'd like to see if these mechanisms also apply to other addictions besides cocaine and morphine. And, we want to move forward to see if this pathway can be used to target addiction."