cocaine self-administration) with brain region group as a repeate

cocaine self-administration) with brain region group as a repeated measure. These were followed by planned Bonferroni’s tests for multiple comparisons. Statistical significance was considered

at P < 0.05. Animals self-administered cocaine (1.5 mg/kg per injection) for five consecutive days with a daily maximum of 40 total injections (all animals self-administered the maximum each day). Injections were limited to ensure that all animals had the same intake over each self-administration session to control for total intake as a factor in the functional effects of cocaine. Because of this limit on the number of daily injections, animals quickly reached the maximum total daily intake (60 mg/kg) and could not exceed that. However, animals could control the rate of intake over the sessions buy BEZ235 (Fig. 1).

Similar to previous studies this rate increased over the 5-day Daporinad in vitro period (Mateo et al., 2005; Calipari et al., 2012; Ferris et al., 2012). One-way anova revealed a main effect of session (F4,56 = 14.93, P < 0.001). Tukey's post hoc analysis revealed an increase in rate vs. the first session on sessions two (q = 4.216, P < 0.05), three (q = 5.843, P < 0.01), four (q = 8.734, P < 0.001) and five (q = 9.673, P < 0.0001). Following cocaine self-administration, behavioral activity was assessed using automated monitors. Our a priori hypothesis was that locomotor activity in response to a novel environment would be reduced following cocaine self-administration (Koeltzow & White, 2003). Two-way anova revealed a main effect of Acesulfame Potassium cocaine self-administration on the response to a novel environment (F1,75 = 4.04, P < 0.05). In addition, there was a main effect of time (F5,75 = 73.53, P < 0.0001) as animals habituated to the activity chamber. There were no significant differences between the groups in either stereotypy or vertical activity. Bonferroni's tests for multiple comparisons were performed

to compare across treatment groups, and a reduction in locomotor activity was observed at the 15-min time point in animals that had undergone cocaine self-administration (t = 3.219, P < 0.05; Fig. 2). Alternatively, we found a significant effect of time (F17,204 = 17.64 P < 0.001), but not of treatment (F1,204 = 0.05, NS) or an interaction (F17,204 = 8.93, NS) on saline-induced locomotion, indicating that normal forward locomotion was not impaired by a prior cocaine self-administration history (Fig. 3). To determine whether other measures of locomotor behavior had changed as a consequence of cocaine self-administration and withdrawal, we assessed vertical activity and stereotypy-like behavior. Student’s t-test revealed that cocaine self-administration animals had higher vertical counts as compared with controls (t12 = 7.604, P < 0.0001; Fig. 4). In addition, cocaine self-administration animals had lower stereotypy counts as compared with controls (t12 = 3.988, P < 0.0001; Fig. 4).

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