Behavioral Mechanisms That Depend on Dopamine and Serotonin in Caenorhabditis elegans Interact With the Antipsychotics Risperidone and Aripiprazole
Abstract
The neurotransmitters dopamine and serotonin participate in specific behavioral neuromuscular mechanisms in the nematode Caenorhabditis elegans. Dopamine is involved in the gentle touch response and serotonin in the pharyngeal pumping rate. In its genome, the worm presents genes encoding dopamine and serotonin receptors orthologous to those of human genes. Risperidone and aripiprazole are a class of drugs known as atypical antipsychotics commonly used to treat schizophrenia, bipolar disorder, and irritability associated with autism. Risperidone is an antagonist of the dopamine D2 and serotonin 5-HT2A receptors. Aripiprazole functions as a partial agonist of the dopamine D2 receptor and as a partial agonist and antagonist of 5-HT1A and 5-HT2A serotonin receptors, respectively. Our results show that risperidone and aripiprazole alter the touch response and pharyngeal pumping in wild-type worm animals. Furthermore, in the presence of the drugs, both behaviors change to varying degrees in dopamine (dop-1, dop-2, and dop-3), serotonin (ser-1), and tyramine (ser-2) receptor-deficient mutants. This variation in response reveals specific targets for these antipsychotics in the nematode. Interestingly, their effect on behavior persisted...Continue Reading
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