How kappa opioid receptors drive anxiety

How kappa opioid receptors drive anxiety

Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. 

Researchers uncovered a cellular mechanism by which kappa opioid receptors (KOR) drive anxiety. These proteins inhibit the release of the neurotransmitter glutamate from basolateral amygdala (BLA), a part of the brain that regulates emotion to the bed nucleus of the stria terminalis (BNST). KORs have been of great interest as a drug target for the treatment of addiction and anxiety disorders.

Authors identify a frequency-dependent, optically evoked local dynorphin-induced heterosynaptic plasticity of glutamate inputs in the BNST. They find that there is cell type specificity to the KOR modulation of the BLA-BNST input with greater KOR-mediated inhibition of BLA dynorphin-expressing neurons.

"When KORs are inactivated, glutamate is released properly and mice showed significant signs of feeling less anxious," said the author. "But when kappa opioid receptors are activated, this glutamate release associated with 'safety' was tamped down. There were clear signs of more anxiety. So, in essence, KORs shut off an anxiety-reducing pathway in the brain."

Humans also have kappa opioid receptors that work in the same way. Several pharmaceutical companies are already working on developing KOR antagonists as a treatment for anxiety and drug abuse, author said. The new study in Cell Reports adds to a growing body of literature showing how these drugs may work.


http://news.unchealthcare.org/news/2016/march/unc-researchers-uncover-how-kappa-opioid-receptors-drive-anxiety

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