Acute behavioral effects of deliriant hallucinogens atropine and scopolamine in adult zebrafish

Atropine and scopolamine are classical muscarinic cholinergic antagonists that exert multiple CNS effects. Belonging to a group of deliriant hallucinogens, these drugs induce delirium-like hallucinations, hyperactivity, altered affective states and amnesia. However, as deliriants remain the least studied group of hallucinogens, their complex and poorly understood profiles necessitate further clinical and preclinical studies. The zebrafish (Danio rerio) is rapidly emerging as a powerful model organism for translational neuropsychopharmacology research. Here, we characterize acute behavioral effects of atropine (60, 90 and 120 mg/L) and scopolamine (60, 120, 180 and 240 mg/L) in adult zebrafish subjected to the novel tank (NTT), light-dark (LDT) and shoaling tests. Overall, atropine at 90 mg/L only mildly increased the NTT locomotor activity, scopolamine at 120 mg/L produced anxiogenic-like NTT effects without affecting other behaviors, and both drugs similarly disrupted zebrafish group behavior in the shoaling test. Collectively, this supports complex and partially overlapping deliriant-like effects of acute atropine and scopolamine in zebrafish. The behavioral sensitivity to these drugs suggests zebrafish as potential screens for cholinergic deliriant psychotropic agents, also necessitating further cross-species in-vivo experimental studies.