Haloperidol Interactions with the dop-3 Receptor in Caenorhabditis elegans

• Published in: Molecular neurobiology Vol. 58; no. 1; pp. 304 - 316
• Main Authors: Krum, Bárbara Nunes, Martins, Airton C., Queirós, Libânia, Ferrer, Beatriz, Milne, Ginger L., Soares, Félix Alexandre Antunes, Fachinetto, Roselei, Aschner, Michael
• Format: Journal Article
• Language: English
• Published: New York Springer US 2021; Springer Nature B.V
• Subjects: Acetylcholine; Antipsychotics; Biomedical and Life Sciences; Biomedicine; Caenorhabditis elegans; Cell Biology; Dopamine D2 receptors; Gene expression; Haloperidol; Life span; Locomotion; Mental disorders; Nematodes; Neurobiology; Neurology; Neuromodulation; Neurosciences; Neurotransmitters; Octopamine; Psychotropic drugs; Signal transduction; Withdrawal; Worms; γ-Aminobutyric acid; Neurotransmitter; Worm; Basal slowing response; Lifespan; Dopamine signaling; Locomotor behavior
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-020-02124-9

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 in
Caenorhabditis elegans
(
C. elegans
) and, its signaling have been associated with alterations in behavioral, molecular, and morphologic properties in
C. 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
, and
dop-3
gene 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 the
dop-3
receptor plays an important role in the effects of haloperidol.