6B. All animals acquired instrumental responding as shown by a significant effect of day (F7,63 = 10.51, P < 0.0001). Although the rate of responding was significantly lower on day 1 than all other days

of operant conditioning (Tukey; all P-values < 0.001), responding rapidly leveled off and was maintained at this rate selleck for the remaining 7 days of training. There was no main effect of future cocaine treatment, nor an interaction of treatment by day. Cocaine self-administration.  Following Pavlovian and instrumental conditioning, rats were trained on either a cocaine or water self-administration procedure over 14 days. During training, complications with catheter patency prevented some cocaine-administering rats from completing all days of training (n = 3), and these rats were not used in subsequent analyses. Across the last 3 days of training, successful cocaine self-administering rats (n = 3) showed stable Selleck Cobimetinib responding, completing 35.8 ± 4.9 responses with a mean intertrial interval of 3.7 ± 0.4 min. Yoked control rats equipped with electrophysiological arrays (n = 3) received the same amount of saline via the catheter as the paired cocaine self-administering rats. However, rats

in the control group nosepoked to receive water reinforcements. Due to the large variability across saline-treated animals, a two-way anova indicated no significant differences between the cocaine and water self-administering groups for the number of all nosepokes (F1,4 = 2.72, P = 0.17), nor an effect of day (F13,52 = 1.6, P = 0.10) or interaction of group × day (F13,52 = 1.6, P = 0.10). Pavlovian-to-instrumental

transfer.  Finally, rats were run on PIT (Fig. 6C). Across all subjects, Selleckchem Decitabine there was a main effect of cue (F2,5 = 17.66, P < 0.001). A Tukey test showed that lever pressing during the CS+ was significantly greater than during the CS− (P < 0.002) and the baseline (P < 0.001). A significant interaction of treatment × cue (F1,6 = 5.48, P < 0.001) revealed that there was a modest trend towards an increase in the rate of lever pressing during the CS+ compared with the baseline in the saline control group (Tukey; P = 0.07; other comparisons not significant), whereas, in contrast, cocaine-treated animals showed a significant difference between the CS+ and baseline (Tukey; P < 0.005) and between CS+ and CS− (Tukey; P < 0.01). Further, although there were no differences in lever-pressing rates between the treatment groups during baseline (Tukey; P = 0.23), the cocaine group pressed significantly more during the CS+ than the saline group (Tukey; P < 0.001). Similar to lever-pressing behavior, rats showed an enhanced foodcup response during the CS+ compared with the CS− and baseline. Specifically, a main effect of cue (F2,12 = 7.88, P < 0.01) revealed a significant increase in foodcup entries during the CS+ compared with the CS− (Tukey; P < 0.02) and baseline (Tukey; P < 0.