Could dental fear have a knockout cure in the future? Researchers at Boston Children's Hospital have identified a new, targeted potential anxiety treatment in a study performed on mice. Over 30 percent of Americans suffer from clinical anxiety in their daily lives, and even more experience a significant degree of fear when visiting their dentist. Mental health professionals across the country cite a 'dire need' for more effective anxiety treatments with fewer side effects, and a new study may provide a direction.
A previous research project had identified certain neurons in the hypothalamus area of the brain play a central role previously unknown in triggering anxiety. Therefore, a targeted approach delivering treatment only to these areas may be more effective than the whole-brain treatment carried out with conventional anxiolytics.
The team at Children's investigated the effect of selectively blocking Corticotropin-Releasing Hormone (CRH) in hypothalamus neurons in mice. Previous research indicated that the reason whole-brain CRH-blocking drugs are ineffective may be because CRH performs different functions in different parts of the brain, so the research team genetically engineered mice to be deficient in CRH in around 1000 nerve cells in the paraventricular nucleus, an area of the hypothalamus associated with stress hormone release.
These CRH-knockout mice as well as a control group were then tested in a type of maze containing elevated platforms, brightly lit areas, and new objects the mice had not previously encountered. These methods are well-established ways to assess the level of anxiety or fear mice experience, as normally their evolutionary conditioning causes them to avoid bright areas, exposed locations, and approach new objects with caution. The degree of anxiety about these features can be quantified by the number of discrete fear behaviors including vigilance, suspicion and freezing.
The researchers reported a "robust finding" in that mice with the CRH knockout were much less inhibited across nearly every metric than the control mice, spending significantly more time on elevated platforms, in the center of open fields, and exploring brightly lit areas with new objects. The control mice did not investigate elevate platforms, stayed to the periphery of open fields and preferred to avoid brightly lit areas.
Further investigation revealed that the effects of CRH inhibition at this small locus in the hypothalamus spread to areas beyond the hypothalamus as well, including areas associated with behavioral stress responses. While replicating this effect only in select neurons in humans could be difficult, it could also represent a potential breakthrough cure for both situational and chronic anxiety. The researchers hope to continue investigating methods of administration and exact mechanism of these results.
Source:
Boston Children's Hospital. (2016, September 6). A New Angle on Anxiety. Retrieved September 12, 2016, from http://www.eurekalert.org/pub_releases/2016-09/bch-ana083116.php
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