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. 2013 Dec 17;3(12):e338. doi: 10.1038/tp.2013.105

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Copyright © 2013 Macmillan Publishers Limited

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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dcc conditional mice exhibit blunted behavioral responses to amphetamine only in adulthood. (a) There were no differences across genotypes in locomotor activity, either at baseline (dcc^lox/lox: n=11; dcc^lox/+DAT^cre: n=12; dcc^lox/loxDAT^cre: n=7; two-way repeated measures ANOVA, no significant main effect of genotype: F_(2,26)=0.1123, P=0.894; no significant interaction: F_(4,52)=0.996, P=0.418) or following a single injection of saline (two-way repeated measures ANOVA, no significant main effect of genotype: F_(2,26)=0.481, P=0.623; no significant interaction: F_(16,208)=0.786, P=0.70). However, dcc conditional mice (dcc^lox/+DAT^cre and dcc^lox/loxDAT^cre) exhibited reduced locomotor activity following an acute injection of amphetamine relative to dcc-floxed control littermates (two-way repeated measures ANOVA, significant main effect of genotype: F_{(2, 27)}=6.747, P=0.0042; significant interaction: F_{(40, 540)}=5.104, P<0.0001). (b) Remarkably, juvenile dcc conditional mice did not exhibit blunted responses to amphetamine. No significant differences were observed across genotypes in locomotor activity at baseline (two-way repeated measures ANOVA, no significant main effect of genotype: F_{(2, 42)}=0.528, P=0.597; no significant interaction: F_(4,42)=1.085, P=0.376), following a single injection of saline (two-way repeated measures, no significant main effect of genotype: F_(2,168)=0.912, P=0.417; no significant interaction: F_(16,168)=0.979, P=0.481), or following a single acute injection of amphetamine (two-way repeated measures ANOVA, no significant main effect of genotype: F_{(2, 420)}=1.072, P=0.36; no significant interaction: F_{(40, 420)}=0.894, P=0.657). (c) dcc conditional mice exhibited resilience to amphetamine-induced deficits in sensorimotor gating. dcc-floxed littermate controls exhibited an impairment in pre-pulse inhibition at lower pre-pulses following an amphetamine (2.8 mg kg⁻¹) challenge (dcc^lox/lox_amph: n=10, dcc^lox/lox_saline; n=9 two-way repeated measures ANOVA, main effect of treatment: F_(1,17)=1.68, P=0.212; significant interaction: F_{(17, 85)}=3.01, P=0.0149. A post hoc ANOVA test for simple effects indicated a significant effect of treatment at the 5 db prepulse (F_(1,102)=4.48, P=0.0443). However, amphetamine did not produce a deficit in prepulse inhibition in dcc^lox/⁺DAT^cre or dcc^lox/loxDAT^cre mice (dcc^lox/+DAT^cre_amph: n=8, dcc^lox/+DAT^cre_saline: n=9; two-way repeated measures ANOVA, no main effect of treatment: F_(1,15)=0.0, P=0.987, no significant interaction: F_(5,75) =.78, P=0.569; dcc^lox/loxDAT^cre_amph: n=8, dcc^lox/loxDAT^cre_saline: n=8; two-way repeated measures ANOVA, no main effect of treatment: F_(1,14)=0.31, P=0.588, no significant interaction: F_(5,70)=2.03, P=0.085).