Researchers from the Max Planck Institute of Psychiatry have discovered two opposing neuronal regulatory circuits behind the generation and elimination of fear.
Both are controlled by the stress-inducing messenger substance corticotropin-releasing hormone (CRH) and its type 1 receptor (CRHR1).
The availability of these factors in neurons that release glutamate in brain areas of the limbic system activates a neuronal network, which causes anxiety behaviour.
Conversely, in dopamine-releasing neurons in the mid-brain, these factors give rise to behaviour that reduces fear.
Using immunohistochemical methods and a series of transgenic mouse lines, the researchers succeeded in mapping the gene activity of the type 1 CRH receptor in the mouse brain in detail for the first time.
The functional examination of the mice gave rise to the fairly sensational discovery that the stress hormone CRH actually reduces fear through its receptors in this part of the brain.
These neurons demonstrably trigger the direct release of dopamine in regions of the forebrain and hence cause behaviour that overcomes fear.
The opposing effects of the fear-generating and fear-eliminating effect of the CRH/CRHR1 was demonstrated for the first time by this study and prompted the re-evaluation of the use of CRH-receptor antagonists as anxiolytic and antidepressant drugs.
The authors speculate that the over-activity of the CRH system in patients with mood disorders is not general but probably limited to certain regulatory circuits in the brain, thus causing imbalanced emotional behaviour.
"The use of CRH-receptor 1 antagonists could be particularly useful in patients in who one of these systems is out of sync," said research group leader Jan Deussing.