Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

Abstract

Background: The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors.

Methods: C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine.

Results: Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice.

Conclusions: Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine.

Figure 1

Timeline of the place preference study.

Figure 2

Initial bias for each chamber of the three-chamber place preference apparatus during the pre-test session. All strains were included in the analysis. Separate analysis excluding 129 mice yielded similar results (data not shown). Error bars are SEM. ***p < 0.001.

Figure 3

Cocaine-induced place preference in six inbred strains. Percent time spent in the cocaine-paired chamber both pre- (white bars) and post-conditioning (grey bars) is shown. Error bars are SEM. *p < 0.05, **p < 0.01.

Figure 4

Acute locomotor response across strains to a single 20 mg/kg cocaine challenge. Saline locomotor activity (white bars) was recorded on day 2 of testing and cocaine locomotor activity (grey bars) was recorded on day 3. Error bars are SEM. **p < 0.01, ***p < 0.001.

Figure 5

Cocaine locomotor sensitization across strains. Locomotor activity for 30-minute sessions across eight days of conditioning. Saline treatment days (white bars) and cocaine treatment days (grey bars) are shown. Error bars are SEM. *p < 0.05.

Figure 6

Effect of training chamber on locomotor activity during repeated exposures to either cocaine or saline. Bars represent locomotor activity of groups of mice (N = 4 per strain; B6 N = 8) exposed to cocaine and saline in either the black or white chamber. The first white bar is cocaine-induced activity in white chambers. The second white bar is saline-induced activity in white chambers. Error bars are SEM. B6, C3H and FVB exhibited more locomotor activity in the black chamber regardless of treatment with either saline or cocaine. D2 mice showed no difference in activity in either black or white chambers. 129 mice showed reciprocal differences in activity and were more active in the black chamber after exposure to cocaine and more active in the white chamber after exposure to saline. BALB mice showed similar amounts of locomotor activity in response to saline in both the black and white chambers and showed a significantly higher response to cocaine only when it was administered in the white chamber.

Figure 7

White vs. black chamber effect on cocaine-induced locomotor activity and sensitization observed for BALB/cJ mice in the CPP apparatus. Results are separated by chamber in which mice received cocaine during conditioning trials. Conditioning days and treatment are shown sequentially along the x-axis. Error bars are SEM.