| Autor: |
Krum BN; Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil.; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA., Martins AC Jr; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA., Queirós L; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.; Department of Biology and CESAM (Centre for Environmental and Marine Studies), University of Aveiro, 3810-193, Aveiro, Portugal., Ferrer B; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA., Milne GL; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, 37240, USA., Soares FAA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.; Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil., Fachinetto R; Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil., Aschner M; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Yeshiva University, Forccheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. michael.aschner@einsteinmed.org. |
| Abstrakt: |
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. |
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