Cross-talk between two compounds ― serotonin and corticotrophin-releasing factor ― is important to control anxiety-like behaviour in mice reports a study published online this week in Nature Neuroscience.
Both corticotrophin-releasing factor (CRF) and serotonin signaling have been implicated in anxious behavior, but it was previously unknown how these two pathways may interact at a cellular level to regulate anxiety.
Stephen Ferguson and colleagues used molecular and biochemical techniques to show that the corticotrophin-releasing factor type 1 receptor (CRFR1) forms a complex with the type 2 serotonin receptor (5-HT2) in mouse neurons. The CRFR1 receptor "helps" the 5-HT2 receptors that have been recycled inside the neuron get back to the neuron's surface. To demonstrate the behavioural relevance of this interaction, the authors injected CRF into the prefrontal cortex of mice, and followed this with an injection of a 5-HT2 receptor agonist. These mice showed an increase in anxiety-like behaviours. However, these compounds had no effect on the mice's behavior when each compound was administered alone, suggesting that the specific interaction between the CRFR1 and 5-HT2 receptor led to the increase in anxiety-like behavior.