Roles of the 5-HT1A receptor in zebrafish responses to potential threat and in sociality

Anxiety is a normal emotion representing a reaction to potential danger, whereas fear can be defined as a reaction to real, explicit danger. Anxiety-like behavior in animal models has been associated with differences in the serotonergic system. Treatment of zebrafish cohorts with 8-OH-DPAT, a full agonist at the 5-HT1A receptor, decreased anxiety-like behavior in the novel tank test, but increased it in the phototaxis (light-dark preference) assay, both considered assays for anxiety-like behavior for this species. The same treatment decreased social approach in both the social investigation and social novelty phases of the social preference test. Blocking the 5-HT1A receptor with WAY 100,635 shifted the dose-response curve for the novel tank test rightward. These effects suggest a participation of the 5-HT 1A heteroreceptors in zebrafish anxiety and social preference, increasing anxiety and decreasing sociality. Thus, the study of this receptor is important for a better understanding of anxiety-like behavior in zebrafish and its relationship with similar phenomena in vertebrates. Preprint: https://www.biorxiv.org/content/10.1101/2024.04.17.588464v1 Data: https://github.com/lanec-unifesspa/5HT/tree/main/5HT1A Lay summaryThis study looked at how a certain type of protein, the 5-HT1A receptor, affected anxiety in zebrafish. Its important to understand that anxiety is a normal feeling we all get when were worried or scared about something, while fear is a reaction to an immediate danger. The researchers wanted to see how a specific drug that activates the 5-HT1A receptor, 8-OH-DPAT, affected the behavior of the fish. They used different tests to see how the fish reacted in different situations. When the fish were given the drug, their anxiety-like behavior decreased in one test where they were put in a new tank. But in another test where they had to choose between light and dark areas, their anxiety-like behavior actually increased. It also made the fish less interested in being social with other fish. When a drug that blocks the 5-HT1A receptor, WAY 100,635, was give together with 8-OH-DPAT, evidence was found for a receptor reserve. The researchers found that this drug affected the way the fish behaved in these situations. It seemed to make them more anxious in some cases and less interested in being social. This tells us that the receptor has an impact on how the fish are feeling, which can help us learn more about anxiety in zebrafish and, potentially, in other animals too, including humans. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/588464v3_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@14b3f13org.highwire.dtl.DTLVardef@11a2217org.highwire.dtl.DTLVardef@b42602org.highwire.dtl.DTLVardef@12b51c4_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance statementThis research indicates that 5-HT1A heteroreceptors play a key role in increasing anxiety and decreasing sociality across vertebrates, shedding light on neural mechanisms that could inform treatments for anxiety-related disorders.