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Fingerprinting of psychoactive drugs in zebrafish anxiety-like behaviors.

Maximino C, da Silva AW, Araújo J, Lima MG, Miranda V, Puty B, Benzecry R, Picanço-Diniz DL, Gouveia A, Oliveira KR, Herculano AM - PLoS ONE (2014)

Bottom Line: The observed phenotypes were clustered according to shared behavioral effects.Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover.These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Neurociências e Comportamento "Frederico Guilherme Graeff", Departamento de Morfologia e Ciências Fisiológicas, Centro de Ciências Biológicas e da Saúde, Universidade do Estado do Pará, Marabá, Pará, Brazil.

ABSTRACT
A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.

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Effects of (A) buspirone, (B) diazepam and (C) caffeine on time on white (upper left), risk assessment (upper right), thigmotaxis (lower left), and freezing (lower right).Bars represent standard error of the mean, and whiskers represent the 2.5 and 97.5 percentile. *, p<0.05; **, p<0.01; ***, p<0.001.
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pone-0103943-g002: Effects of (A) buspirone, (B) diazepam and (C) caffeine on time on white (upper left), risk assessment (upper right), thigmotaxis (lower left), and freezing (lower right).Bars represent standard error of the mean, and whiskers represent the 2.5 and 97.5 percentile. *, p<0.05; **, p<0.01; ***, p<0.001.

Mentions: Given the diversity of potential drug effects in the different behavioral parameters, a “behavioral fingerprint” was assigned to each compound and dose by determining the Maximum Predictive Value [15], [43] for each effect and applying clustering algorithms to organize behavioral parameters and molecules [44]. This analysis allowed the organization of the data set broadly into anxiolytic, anxiogenic, and motor stimulating, identifying four clusters which correspond to “avoidance” (Time on white and Thigmotaxis), “locomotor” (Entries in white and Midline crossings), “risk assessment” (Latency to white, Risk assessment and Erratic swimming) and “fear” (Freezing) measures (Figure 1). For example, buspirone and diazepam produced a marked anxiolytic-like effect – increasing time spent in the white compartment and decreasing risk assessment, thigmotaxis and freezing in the white compartment (Figures 2A and 2B) –, while caffeine had an opposite profile (Figure 2C).


Fingerprinting of psychoactive drugs in zebrafish anxiety-like behaviors.

Maximino C, da Silva AW, Araújo J, Lima MG, Miranda V, Puty B, Benzecry R, Picanço-Diniz DL, Gouveia A, Oliveira KR, Herculano AM - PLoS ONE (2014)

Effects of (A) buspirone, (B) diazepam and (C) caffeine on time on white (upper left), risk assessment (upper right), thigmotaxis (lower left), and freezing (lower right).Bars represent standard error of the mean, and whiskers represent the 2.5 and 97.5 percentile. *, p<0.05; **, p<0.01; ***, p<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4117595&req=5

pone-0103943-g002: Effects of (A) buspirone, (B) diazepam and (C) caffeine on time on white (upper left), risk assessment (upper right), thigmotaxis (lower left), and freezing (lower right).Bars represent standard error of the mean, and whiskers represent the 2.5 and 97.5 percentile. *, p<0.05; **, p<0.01; ***, p<0.001.
Mentions: Given the diversity of potential drug effects in the different behavioral parameters, a “behavioral fingerprint” was assigned to each compound and dose by determining the Maximum Predictive Value [15], [43] for each effect and applying clustering algorithms to organize behavioral parameters and molecules [44]. This analysis allowed the organization of the data set broadly into anxiolytic, anxiogenic, and motor stimulating, identifying four clusters which correspond to “avoidance” (Time on white and Thigmotaxis), “locomotor” (Entries in white and Midline crossings), “risk assessment” (Latency to white, Risk assessment and Erratic swimming) and “fear” (Freezing) measures (Figure 1). For example, buspirone and diazepam produced a marked anxiolytic-like effect – increasing time spent in the white compartment and decreasing risk assessment, thigmotaxis and freezing in the white compartment (Figures 2A and 2B) –, while caffeine had an opposite profile (Figure 2C).

Bottom Line: The observed phenotypes were clustered according to shared behavioral effects.Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover.These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Neurociências e Comportamento "Frederico Guilherme Graeff", Departamento de Morfologia e Ciências Fisiológicas, Centro de Ciências Biológicas e da Saúde, Universidade do Estado do Pará, Marabá, Pará, Brazil.

ABSTRACT
A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.

Show MeSH