Hallucinogenic compounds produce a wide spectrum of behavioral and cognitive effects in humans and animals. Although the use of these drugs predates written history, their behavioral and physiological effects have not been fully elucidated. Zebrafish (Danio rerio) emerge as a novel model organism highly sensitive to hallucinogenic substances. This study examines the effects of two potent, pharmacologically distinct hallucinogenic compounds (mescaline and salvinorin A) on adult zebrafish tested in a variety of behavioral paradigms. Additionally, neuroendocrine and gene expression assays were preformed in order to assess potential biomarkers of zebrafish physiological responses to these drugs. Despite its rapid prominent clinical effects, salvinorin A at acute doses tested (5–50 mg/l) produced very few effects in the novel tank test, albeit affecting the group social behavior in the shoaling test. At all doses tested, zebrafish whole-body cortisol levels and c-fos expression were unaltered following salvinorin A treatment. In contrast, mescaline (5–20 mg/l) dose-dependently affected novel tank behavior, significantly increasing top swimming activity and disrupting the normal patterning of zebrafish swimming behavior. Mescaline also significantly altered zebrafish social behavior in both the shoaling and social preference tests, and decreased cortisol levels while increasing brain c-fos expression. Additionally, we developed a novel method of zebrafish neurophenotyping, and applied it here to generate 3D spatiotemporal reconstructions of zebrafish swimming trajectories in the novel tank test showing that zebrafish swimming patterns were affected by the two hallucinogenic agents tested. Collectively, these findings demonstrate the sensitivity of adult zebrafish to hallucinogenic agents and should foster future investigations into the behavioral and physiological correlates of the drug evoked psychedelic states.
|Advisor:||Kalueff, Allan V.|
|Commitee:||Hebert, Thomas, Schrader, Laura|
|School:||Tulane University School of Science and Engineering|
|School Location:||United States -- Louisiana|
|Source:||MAI 50/06M, Masters Abstracts International|
|Subjects:||Neurosciences, Psychobiology, Pharmacology|
|Keywords:||Cortisol, Mescaline, Salvinorin a, Social behavior, Three-dimensional neurophenotyping, Zebrafish|
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