Automated gait analysis in mice after administration of an acute toxic dose of methamphetamine and treatment with modafinil.

BISAGNO V; SMITH K; URBANO FJ; CUSTER CE; MYAL S; LOZAMA A; PRISINZANO TE; FANTEGROSSI WE; RANDOLPH M; GARCIA-RILL E

Washington DC, USA, Nov 12-16, 2011

Congreso; 41th Society for Neuroscience Annual Meeting; 2011

Society for Neuroscience

Recent findings indicate that the motor consequences of even brief exposures to methamphetamine (METH) can persist long after the stimulant is discontinued. In mice, an acute dose of METH (3 injections at 7 mg/kg, 3 h apart, measured six days after last injection) induced striatal neurotoxicity that might affect locomotor activity (see Raineri et al., SFN 2011). Modafinil is an anti-narcoleptic drug that is used off-label to treat psychostimulant addiction and that might also possess some neuroprotective properties against METH toxicity. Several assisted automated gait analysis systems provide a comprehensive method to assess a number of dynamic and static gait parameters simultaneously. In this study, we used Catwalk (Noldus Inc.) to investigate gait parameters in Swiss Webster male mice following an acute METH binge (3 injections at 7 mg/kg, 3 h apart), with and without modafinil treatment (2 injections at 90 mg/kg, 1 h before the first and third METH injection). Initially, results obtained with animals that received just one training session in CatWalk indicated that the group that received only METH showed increases in total time to complete the run and number of steps, and decreased speed (measured six days after last METH). In a second experiment, other groups of mice received two training sessions per day for three days before baseline runs. Six days after injection with METH and/or modafinil mice were again tested. Under these new conditions, we found only small differences in METH treated subjects (e.g. base of support or the average width between either the front or the hind paws), suggesting that, after training in the CatWalk apparatus, the effects of METH were less robust. Moreover, our results also show that having a baseline for each of the experimental groups is helpful to eliminate possible random differences in locomotion and suggest that persistent effects of METH are more pronounced on unfamiliar/unpracticed motor behaviors. Thus, the utility of automated gait systems for the study of the motor effects of psychostimulants will be discussed in the context of subtle locomotor effects, and possible anorexic effects (which might decrease body weight), generating confounding results of gait analysis.