Acute locomotor responses to cocaine in adolescents vs. adults from four divergent inbred mouse strains

Abstract

Growing evidence suggests that adolescent mice display differential sensitivity to the acute locomotor activating effects of cocaine as compared to adults, but the direction of the difference varies across studies and the reasons are not clear. Few studies have directly examined genetic contributions to age differences in locomotor stimulation from cocaine. The goal of this study was to determine the extent to which reduced stimulation in C57BL/6J adolescents as compared to adults generalizes to other strains. Therefore, we examined male and female mice from four genetically divergent inbred stains (BALB/cByJ, C57BL/6J, DBA/2J and FVB/NJ) at two ages, postnatal day 30 and postnatal day 65. Mice received either saline or cocaine (15 or 30 mg/kg), and then immediately were placed back into their home cages. Locomotor activity was recorded continuously in the home cage by video tracking. Adolescents displayed reduced stimulation as compared to adults for C57BL/6J, BALB/cByJ and female FVB/NJ mice. No age differences were observed for DBA/2J or male FVB/NJ. No main effects of sex were observed. Strain differences in pharmacokinetics, neural development or physiology could contribute to the observed differences between ages across strains. Future comparative studies could discover biological differences between strains that explain age differences in cocaine sensitivity.

Figure 1

Photograph of the custom-made home cages where animals were tested for cocaine-induced locomotor stimulation by continuous overhead video tracking. Note that FVB/NJ and BALB/cByJ were tested in cages with dark type bedding (Shepherd Paperchip®) whereas C57BL/6J and DBA/2J were tested with light colored bedding (Harlan Corncob) to facilitate video tracking (dark object on light background or light object on dark background). Red light was used to illuminate the cages during the dark cycle when locomotor activity testing occurred.

Figure 2

Average (± SE) distance traveled summed over 60 min following acute i.p. injection of saline or cocaine. Each bar represents the average of 8 individuals (collapsed across sex; 4 males, 4 females). Adults are shown as solid bars and adolescents open bars.

Figure 3

Comparison of female and male BALB/cByJ mice following 30 mg/kg cocaine. Average distance traveled in 5 min bins (± SE) is plotted against time for adults (filled symbols) and adolescents (open symbols). Animals were given a saline injection at 60 min, and 30 mg/kg cocaine injection at 120 min. Each data point represents the average of 4 individuals. Both graphs share the same y-axis.

Figure 4

Comparison of female and male FBV/NJ mice following cocaine injection. Average (± SE) distance traveled summed over 60 min following acute i.p. injection of saline or cocaine plotted separately for adults (solid bars) and adolescents (open bars). Each bar represents the average of 4 individuals. Both graphs share the same y-axis.