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GABA neurons could be a therapeutic target for neuropsychiatric diseases

Research conducted on the role GABA neurons play in the ventral tegmental area of the midbrain could result in new treatment methods for individuals with certain mental illnesses, researchers report.

Neuroscientists at the University of North Carolina, Chapel Hill, led by Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and Molecular Physiology, reported their findings in the journal Neuron. Stuber and colleagues determined, they say for the first time, that activation of the nearby ventral tegmental area (VTA) GABAergic neurons directly inhibited the function of dopamine (DA) neurons. By activating these brain cells, researchers suppressed the pleasure and reward response associated with dopamine release. Dopamine is a chemical messenger that plays a significant role in reward-driven responses and learning.

Using laser technology and fiber optics for optogenetic stimulation, the researchers manipulated GABA neurons in transgenic mice, resulting in the suppression of dopamine. By beaming light via laser into brain tissue and targeting the GABA cells, the researchers tested the animals by activating the cells during a cue period before they were able to drink a sugar water. Researchers also stimulated the cells while the animals were actively drinking the sucrose, and their drinking ceased. Once the stimulus stopped, the animals drank again.

“The dynamic interplay between VTA DA and GABA neurons can control the initiation and termination of reward-related behaviors,” the researchers wrote.

Although it remains unclear why some individuals fail to gain pleasure from activities that normally elicit pleasurable responses, Stuber and his colleagues believe their discovery may lead to new treatments for individuals afflicted by schizophrenia, depression and other mental illnesses.

“A dysfunction in these GABA neurons might potentially underlie different aspects of neuropsychiatric illness, such as depression,” they wrote. “Thus, we could think of them as a new physiological target for various aspects of neuropsychiatric diseases.

Disclosures: Dr. Stuber and colleagues report the study was funded by the Brain & Behavior Research Foundation (NARSAD grant), The Whitehall Foundation, The Foundation of Hope, National Institute on Drug Abuse, and the Department of Psychiatry at the University of North Carolina, Chapel Hill.