In this work, we carried out neurochemical and behavioral analysis of zebrafish (Danio rerio) treated with rotenone, an agent used to chemically induce a syndrome resembling Parkinson's disease (PD). Dopamine release, measured with fast-scan cyclic voltammetry (FSCV) at carbon-fiber electrodes in acutely harvested whole brains, was about 30% of that found in controls. Uptake, represented by the first order rate constant (k) and the half-life (t1/2) determined by nonlinear regression modeling of the stimulated release plots, was also diminished. Behavioral analysis revealed that rotenone treatment increased the time required for zebrafish to reach a reward within a maze by more than 50% and caused fish to select the wrong pathway, suggesting that latent learning was impaired. Additionally, zebrafish treated with rotenone suffered from diminished locomotor activity, swimming shorter distances with lower mean velocity and acceleration. Thus, the neurochemical and behavioral approaches, as applied, were able to resolve rotenone-induced differences in key parameters. This approach may be effective for screening therapies in this and other models of neurodegeneration.

• MeSH
• dánio pruhované metabolismus   MeSH
• dopamin metabolismus   MeSH
• kognice MeSH
• modely nemocí na zvířatech MeSH
• Parkinsonova nemoc * MeSH
• rotenon * farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• dopamin MeSH
• rotenon * MeSH

Alzheimer's disease (AD) is a progressive, fatal, neurodegenerative disorder for which only treatments of limited efficacy are available. Despite early mentions of dementia in the ancient literature and the first patient diagnosed in 1906, the underlying causes of AD are not well understood. This study examined the possible role of dopamine, a neurotransmitter that is involved in cognitive and motor function, in AD. We treated adult zebrafish (Danio rerio) with okadaic acid (OKA) to model AD and assessed the resulting behavioral and neurochemical changes. We then employed a latent learning paradigm to assess cognitive and motor function followed by neurochemical analysis with fast-scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes to measure the electrically stimulated dopamine release. The behavioral assay showed that OKA treatment caused fish to have lower motivation to reach the goal chamber, resulting in impeded learning and decreased locomotor activity compared to controls. Our voltammetric measurements revealed that the peak dopamine overflow in OKA-treated fish was about one-third of that measured in controls. These findings highlight the profound neurochemical changes that may occur in AD. Furthermore, they demonstrate that applying the latent learning paradigm and FSCV to zebrafish is a promising tool for future neurochemical studies and may be useful for screening drugs for the treatment of AD.

• Klíčová slova
• Alzheimer’s disease, behavior, dopamine, fast-scan cyclic voltammetry, okadaic acid, zebrafish,
• MeSH
• Alzheimerova nemoc * MeSH
• dánio pruhované MeSH
• dopamin * MeSH
• karbonové vlákno MeSH
• kyselina okadaová MeSH
• mikroelektrody MeSH
• neurotransmiterové látky MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• dopamin * MeSH
• karbonové vlákno MeSH
• kyselina okadaová MeSH
• neurotransmiterové látky MeSH