• generalized anxiety disorder

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. Of the human HTR2 genes, only Hsap\HTR2C has been introduced into flies; a stock is available but has not been characterized.

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]