Repeated microdoses of LSD do not alter anxiety or boldness in zebrafish.

LSD at low concentrations (1.5, 15, and 150 µg/L) acutely reduced high mobility in zebrafish, and the two lowest concentrations also decreased swimming velocity. However, after repeated daily exposure for ten days followed by a seven-day withdrawal period, no significant differences in anxiety-like behavior, boldness, or locomotion were observed between any LSD-treated group and controls. These results suggest that while LSD can produce acute behavioral effects at very low doses, tolerance may develop with repeated administration, and no lasting behavioral changes persist after withdrawal.

Study at a glance

Abstract

The therapeutic use of lysergic acid diethylamide (LSD) has resurfaced in the last decade, prompting further scientific investigation into its effectiveness in many animal models. Zebrafish (Danio rerio) are a popular model organism in medical sciences and are used to examine the repeated administration of pharmacological compounds. Previous zebrafish research found acute LSD altered behaviour and cortisol levels at high (250 µg/L) but not low (5-100 µg/L) levels. In this study, we used a motion tracking system to record and analyze the movement patterns of zebrafish after acute and repeated 10-day LSD exposure (1.5 µg/L, 15 µg/L, 150 µg/L) and after seven days of withdrawal. The open-field and novel object approach tests were used to examine anxiety-like behaviour, boldness, and locomotion. In the acute experiments we observed a significant decrease in high mobility with 1.5 µg/L, 15 µg/L, and 150 µg/L of LSD compared to the control and a decrease in velocity with 1.5 and 15 µg/L. In repeated experiments, there were no significant differences in the levels of anxiety, boldness, or locomotion between all LSD groups and controls immediately after 10-day treatment or after withdrawal.