The inability to find pleasure in activities that would normally be enjoyable (such as listening to music, social interaction, or even sex) is often a symptom of disorders such as depression and schizophrenia. Known as anhedonia – literally translated as “without pleasure" – the neurological condition is closely related to feelings of hopelessness and isolation. Researchers think that they may have found the brain circuit responsible for this condition in rats after a series of experiments.
Previous studies have found that anhedonia is linked to a region of the brain known as the medial prefrontal cortex (mPFC). This is a part of the brain found, as the name suggests, a little way into the front of the organ, and has also been linked to a range of other functions such as short-term memory and personality. By stimulating this region, the researchers were able to induce feelings of anhedonia in the subject rodents, causing them to lose their preference for sugar water, as well as causing them to socialize less with other rats.
The rodents were genetically engineered so that certain regions of their brain were activated when scientists shone pulses of light onto them. This technique, called optogenetics, uses genetic modification to insert into specific cells a gene that confers light responsiveness to those cells. This means that researchers can in effect “turn on” and “off” target cells, or groups of cells, by simply flashing them with light. For this experiment, published in Science, the researchers conducted two different modifications: one in which they activated engineered regions of the rats’ midbrain involved in reward and dopamine release known as the striatum, and another where they activated the rats' mPFC.
After using lasers to stimulate the striatum, the scientists then performed functional magnetic resonance imaging (fMRI) on the rodents, which showed an increase in blood flow to this region correlating with the increase in dopamine, and thus their enjoyment. When the researchers then stimulated the rats' mPFC and used fMRI on them, they found that the blood flow to the striatum decreased, which correlated with “depressive” behavior in the rodents. This was measured by their preference for either plain water or sugar water, as well as how social they were with other rats.
The researchers also found that when the mPFC was stimulated, the connections to other regions of the brain were also altered. For example, while connections to other parts of the brain associated with reward were strengthened, the pathways to regions of the brain shown to be related to depression and schizophrenia were weakened. This simply goes to show the complexity of the organ, and how nothing associated with how it works is ever straightforward or simple.
It is hoped that by working out how anhedonia is formed and controlled, scientists might one day be able to produce drugs or therapies that could target it, and hopefully break the lack of pleasure cycle often seen with depression and other psychological conditions.
