Using the Drosophila wall-following assay (WAFO; see FBhh0001005), the roles of serotonin class 2 receptors in the modulation of anxiety were assessed. There are two serotonin class 2 receptor genes in flies. Knockdown of Dmel\5-HT2B was observed to significantly increase WAFO (interpreted as increased anxiety); knockdown of Dmel\5-HT2A had no consistent effect. RNAi-targeting constructs, alleles caused by insertional mutagenesis, and an amorphic allele created by targeted recombination have been generated for both Dmel\5-HT2B and Dmel\5-HT2A.
There are three human serotonin class 2 receptor genes. Mutations in the human HTR2A gene are associated with susceptibility to schizophrenia, obsessive-compulsive disorder, and other psychiatric conditions; variants in this gene also affect response to specific antidepressants. None of the human HTR2 genes has been introduced into flies.
The fly 5-HT2A and 5-HT2B genes have not been extensively characterized. As in the WAFO assay, the two genes exhibit different responses in an assay assessing resistance to a drug that suppresses feeding: animals with loss-of-function genotypes of Dmel\5-HT2A are more resistant than wild-type to the drug metitepine, while the response of animals with an amorphic mutation of Dmel\5-HT2B is similar to wild-type. See the human disease model report 'obesity, susceptibility to (postulated), serotonin class 2 receptor(s)' (FBhh0001104).
WAFO experiments using the Drosophila serotonin class 1 receptor gene 5-HT1B are described in the human disease model report 'anxiety modulators, fly wall-following model' (FBhh0001005). Reciprocal effects are observed: knockdown of the fly gene results in increased WAFO, overexpression results in decreased WAFO.
[updated Jul. 2019 by FlyBase; FBrf0222196]