Figure 4.

Selective MOR deletions define specific roles of A2a and ChAT populations in an opioid self-administration profile. A–D, Acquisition. During this short acquisition phase (days 1–4) during which remifentanil was self-administered there was no effect of genotype and no interaction or a main effect of genotype on any of the four parameters measured; active lever presses (A), inactive lever presses (B), reinforcers earned (C), or the percent active lever presses made (D). E–H, Maintenance and extinction. Mice were then transitioned to oxycodone self-administration for 9 d followed by 3 d of extinction. When compared with mice self-administering saline, those that self-administered oxycodone made more active lever presses (p < 0.05), earned more reinforcers (p < 0.05), and showed a preference for the active over inactive lever (p < 0.0001) during the maintenance and extinction session. E, During the extinction but not maintenance phases, A2aflMORs made more active lever presses than flMORs (p < 0.05). F, There was no effect of genotype on the number of inactive lever presses at any stage. G, Similar to the number of active lever presses made, A2aflMORs and ChATflMORs earned more reinforcers than flMORs during extinction (a: p < 0.05). H, There was no effect of genotype on active lever preference as shown by the percent active lever/total lever presses. I–N, Within session analysis of the cumulative number of active lever presses made and reinforcers earned during the 2-h session was assessed on three specific days; the last day of oxycodone (day 9) and the first (day 10) and third (day 12) days of extinction. This shows no effect of genotype on the last day of oxycodone for either the cumulative active lever presses (I) or reinforcers (J) earned. K, However, on the first day of extinction, A2aflMORs made more active lever presses than flMORs (a: p < 0.05 vs flMOR at 103 and 104 and 110–120 min). I, A similar effect was seen in the reinforcers earned during this session when A2aflMORs earned more reinforcers (a: p < 0.05 vs flMOR at 87–99 and 103 min) as did ChATflMORs (b: p < 0.05 vs flMOR at 69–102 min). N, On the third day of extinction, there was no further effect of genotype on the number of active lever presses made. M, However, the ChATflMORs showed an increase in reinforcers earned on the third day of extinction (a and c: p < 0.05 and p < 0.01, respectively, vs flMOR at 82–120 min). Refer to Table 5 for statistical analyses. All data are shown as mean ± SEM.