Haloperidol Interactions with thedop-3Receptor inCaenorhabditis elegans

Haloperidol is a typical antipsychotic drug commonly used to treat a broad range of psychiatric disorders related to dysregulations in the neurotransmitter dopamine (DA). DA modulates important physiologic functions and perturbations inCaenorhabditis elegans(C. elegans) and, its signaling have been associated with alterations in behavioral, molecular, and morphologic properties inC. elegans. Here, we evaluated the possible involvement of dopaminergic receptors in the onset of these alterations followed by haloperidol exposure. Haloperidol increased lifespan and decreased locomotor behavior (basal slowing response, BSR, and locomotion speed via forward speed) of the worms. Moreover, locomotion speed recovered to basal conditions upon haloperidol withdrawal. Haloperidol also decreased DA levels, but it did not alter neither dop-1,dop-2, anddop-3gene expression, nor CEP dopaminergic neurons' morphology. These effects are likely due to haloperidol's antagonism of the D2-type DA receptor,dop-3. Furthermore, this antagonism appears to affect mechanistic pathways involved in the modulation and signaling of neurotransmitters such as octopamine, acetylcholine, and GABA, which may underlie at least in part haloperidol's effects. These pathways are conserved in vertebrates and have been implicated in a range of disorders. Our novel findings demonstrate that thedop-3receptor plays an important role in the effects of haloperidol.

Automated summary

The antagonism of the D2-type DA receptor dop-3 by haloperidol is likely responsible for the effects seen in Caenorhabditis elegans, affecting mechanistic pathways involved in neurotransmitter modulation and signaling, such as octopamine, acetylcholine, and GABA. This finding suggests a potential mechanism underlying the effects of haloperidol, with implications for disorders in both invertebrates and vertebrates.