Researchers identify and successfully activate neurons that tell the brain to stop drinking.
In alcoholism and addictive drugs repeated exposure triggers glutamatergic and GABAergic plasticity in many neuronal populations. The dorsomedial striatum (DMS), a brain region critically involved in addiction, contains medium spiny neurons expressing dopamine D1 or D2 receptors, which form direct and indirect pathways, respectively. However, it is unclear how alcohol-evoked plasticity in the DMS contributes to alcohol consumption in a cell type-specific manner. Now, a study from researchers at the Texas A&M Health Science shows by activating particular neurons, the global medical community may be able to diminish alcohol drinking behaviour. The team state that their findings provide insight into another mechanism underlying alcoholism, with D1 and D2 medium spiny neurons shown to have opposing roles in alcohol consumption. The study is published in the journal Biological Psychiatry.
Previous studies show that the majority of DMS cells are medium spiny neurons that express dopamine D1 receptors or D2 receptors, which drive ‘Go’ or ‘No-Go’ behaviours, respectively. In other words, when D2 neurons are activated, they discourage action, telling the person to wait, to stop, to do nothing. When they are activated, they inhibit drinking behaviour, so activating them is important for preventing problem drinking behaviour. Studies show that, even in individuals without alcoholism, D2 neurons tend to become deactivated when they drink too much. This deactivation means there is nothing telling them to stop drinking. Earlier studies from the lab showed that alcohol consumption alters the physical structure and function of these neurons in the DMS. Essentially, they found that activation of D1 neurons determines whether one drink leads to two. The current study shows that blocking the activity of this neuronal population reduces alcohol intake.
The current study utilises mice that express a fluorescence marker to visualize D1 and D2 neurons, to show that repeated cycles of alcohol or alcohol consumption induces a long-lasting increase in AMPAR activity specifically in DMS D1R but not in D2 neurons. Results show that alcohol consumption increases the complexity of dendritic branching and the density of mature mushroom-shaped spines selectively in DMS D1 neurons. Data findings show that blockade of D1 neurons in the DMS diminishes alcohol consumption.
The group state that together, these data suggest that alcohol intake produces profound functional and structural plasticity events in a subpopulation of neurons in the DMS that control reinforcement-related learning. They go on to add that by manipulating the activity of these neurons, the researchers were actually able to change the alcohol-drinking behaviour of the animal models.
The team surmise that by activating D2 neurons, they were able to decrease alcohol consumption, and the more the D2 neurons were activated, the greater the effect is likely to be. For the future, the researchers state that although they are a long way from testing this in humans, in theory, if they could someday use drugs or electrical stimulation or some other method of activating the D2 neurons, then the global medical community might be able to prevent alcoholics from wanting another drink.