Serotonin Receptors Affect Reaction to Stress

How individuals react to stressful situations and difficult situation could be partly caused by the dominance of one cell-surface marker over another in a brain region involved in controlling emotional responses and behaviors, suggest findings from a new study.

The study was performed by scientists from the University of Pittsburgh (PA, USA). These two markers--both receptors that determine what effect the neurotransmitter serotonin has on a neuron--seem to be major intermediaries influencing emotional state and behavior during stress.

In a localized region of the prefrontal cortex, where thought and action are organized, the number and ratio of serotonin receptors were discovered to be directly associated with the activity of another part of the brain called the amygdala, which is vital for producing emotional states such as fear. According to Ahmad Hariri, Ph.D., who led the study, these findings bring understanding into what could be a essential factor contributing to the development of risk for psychiatric disorders and a significant molecular mechanism to target as new therapies are developed.

The subgenual prefrontal cortex is one region where communication, or cross talk, occurs between the impulsive, reflexive amygdala, and the more logical, serious prefrontal cortex. The study of 18 normal people utilized positron emission tomography (PET), which provides three-dimensional (3D) detail of the distribution of molecular structures. The investigators used PET to assess the availability of the two receptors for serotonin in specific areas of the participants' brains, including the amygdala and subgenual prefrontal cortex. One of these receptors, the 5-HT1A, causes neurons to be inhibited when serotonin binds to it. In contrast, binding the other receptor, the 5-HT2A, causes the cell to be excited.

The same individuals also underwent testing with functional magnetic resonance imaging (fMRI), which illustrates the regions of the brain that are engaged during different tasks. Those individuals in whom PET showed a higher number of serotonin 5-HT1A receptors relative to 5-HT2A receptors in the subgenual prefrontal cortex had less brain activity in this area during fMRI, as would be expected, because 5-HT1A is the inhibitory receptor. The scientists discovered that these specific serotonin receptors seem to help control the extent to which any rational communication takes place in the subgenual prefrontal cortex. Without the voice of reason, the amygdala can act as it chooses.

By evaluating individuals who carry a form of a gene required for determining expression of the serotonin transporter and who, because of this variation, are more susceptible to develop depression when confronted with stressful and difficult life situations, the researchers found less crosstalk in the subgenual prefrontal cortex as well as greater amygdala activity.




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