Effects of antipsychotics on intestinal motility in zebrafish larvae

Background: Antipsychotics are essential for the treatment of schizophrenia. However, due to side effects, both continuity of treatment and patients' general health can be jeopardized. Some of these drugs, especially clozapine, have a class of side effects attributed to their antimuscarinic properties, such as dysmotility, a condition in which muscles of the digestive system become impaired. Dysmotility may also alter the speed, strength or coordination of the digestive organs, causing distention, disturbing gastrointestinal transit, leading to symptoms such as bloating, nausea, vomiting, and even malnutrition. In this study, our aim was to develop an in vivo assay capable of identifying and studying the antimuscarinic effects of antipsychotics in a zebrafish model. Methods: We performed video recordings of in vivo 5-day postfertilization (dpf) zebrafish larvae gastrointestinal tracts and analyzed the frequency of spontaneous and regular cycles of contractions of the gut. Key Results: The assay was first validated with treatment with atropine. We showed that this antimuscarinic drug reduces peristaltic cycles. Subsequently, the larvae were treated with the antipsychotics haloperidol, risperidone, and clozapine. Neither haloperidol nor risperidone reduced gut motility, but clozapine significantly reduced the frequency of cycles of contractions (P<.0001), which confirms the existing clinical data. Conclusions & Inferences: We conclude that this zebrafish assay efficiently identifies anticholinergic side effects of antipsychotics, and can thus be a quick and useful way to screen for this property in new drugs.