A state-of-the-art method for high-throughput, automated locomotor activity testing in neuropharmacology, safety, and toxicology studies

Abstract

The quantification of spontaneous locomotor activity, stereotyped movements, anxiety-related behavior, and exploration parameters is pivotal in neuropharmacology, safety, and neurotoxicity studies to determine whether new chemical entities possess psychostimulant, sedative, or toxic effects. Such studies may involve large-scale assessments of locomotor activity in rodents under GLP compliance, which can be labor-intensive and time-consuming. To address these challenges, we have developed the VivaMARS system for automated, high-throughput (up to 30 subjects by session) locomotor activity testing in rodents. This study aims to validate the VivaMARS platform with two reference compounds: caffeine (CAF), which is known to increase rodent activity, and chlorpromazine (CPZ), which is known to decrease rodent activity. Experiments utilized healthy adult Sprague Dawley® male rats (7–8 weeks old, 250–300 g) and CD1 male mice (six weeks old, 25–30 g). Animals were divided in 5 groups (N = 4 each): saline, low-dose, or high-dose groups for two reference compounds. CAF (low 4 mg/kg and high 16 mg/kg for both mice and rats) and CPZ (low 3 mg/kg and high 10 mg/kg for both mice and rats) were administered intraperitoneally. Data was recorded for 60 min immediately after CAF administration and 30 min after CPZ administration. The parameters quantified were total activity, subdivided into activity with displacement (ActiD) and without displacement (ActiND), distance travelled, vertical activity, immobility time, and speed characterization. Data were acquired and analyzed using the GLP-compliant Ponemah software. Table 1 details the effects of CAF and CPZ on measured parameters in mice and rats. In brief, a dose-dependent effect on ActiD was observed in both species after CAF (increase) and CPZ (decrease) administration. CAF-treated rodents travelled longer and CPZ-treated shorter distances compared to saline. As expected, CAF reduced, and CPZ increased immobility time in both mice and rats. CAF increased vertical activity in both species, while CPZ reduced vertical activity. The average speed was higher in CAF-treated animals and lower in CPZ-treated animals. Our data demonstrates that VivaMARS is a powerful platform for acute locomotor activity testing in rodents. Further experiments are needed for a more comprehensive validation of the instrument.