Subsequently, stimulation was discontinued and responses OSI-906 nmr at the active port had no effect (“extinction”). After a further 30 min had elapsed, brief “priming” stimulation trains were delivered to indicate to the rat that stimulation was once again available (“reacquisition”). We found that Th::Cre+ rats rapidly extinguished and then reacquired responding for DA ICSS, performing significantly fewer active nosepokes during extinction as compared to both maintenance and reacquisition (two-tailed Wilcoxon signed-rank test;

p < 0.01 for maintenance versus extinction, p < 0.05 for extinction versus reacquisition, Figures 6F and 6G). The extinction of active responding was rapid; within 5 min after extinction onset, rats had decreased their average rate of responding at the active nosepoke to less than 10% of the rate sustained during maintenance. Importantly, by the last 5 min of the extinction phase Th::Cre+ rats no longer responded preferentially at the active nosepoke ( Figure 6H), instead responding

at equivalently this website low levels at both active and inactive nosepoke ports. Next, we asked whether the contingency between behavioral responses and optical stimulation was required to sustain responding. Rats were allowed to respond for stimulation over 30 min (“maintenance”), followed by a period of contingency degradation (“CD”) during which stimulation trains were delivered pseudorandomly at intervals matched to the average rate at which they were earned by each rat during FR1 responding in a previous session. Rats could continue to respond at the active port during this phase, but the delivery of stimulation trains occurred independently of these responses. After 30 min had passed, noncontingent stimulation ceased and reinforcement was once again made contingent on responses Vorinostat (SAHA, MK0683) in the active port (“reacquisition”). We found that Th::Cre+ rats were sensitive to degradation of the contingency between response and reinforcement, as they performed significantly fewer active nosepokes during CD than they had during maintenance (two-tailed Wilcoxon signed-rank test,

p < 0.01; Figures 6I and 6J) despite the fact that the number of stimulation trains delivered did not differ across the two epochs (two-tailed Wilcoxon signed-rank test, p > 0.05, Figure 6J). Interestingly, by the last 5 min of the CD phase Th::Cre+ rats still showed a small but significant preference for responding at the active nosepoke ( Figure 6K). Additionally, on average rats increased responding at the active port during reacquisition, although when summed across the 30 min epoch this change was not statistically significant (two-tailed Wilcoxon signed-rank test, p > 0.05; Figure 6J). Together, the extinction and contingency degradation manipulations demonstrate that the robust maintenance of Th::Cre+ rat responding at the active port arises from response-contingent optical stimulation of DA neurons.