Fig. 2
The long-term therapeutic effect of U50 on cue-induced reinstatement depends on extinction day 1 training and signaling through p38 MAPK. Following 2 weeks of cocaine self-administration and 7 days of home cage abstinence, rats were administered a single dose of U50 (5 mg/kg, i.p.) 30 min prior to the first extinction session, or in the home cage (U50-HC; n = 8). Extinction groups received vehicle (n = 6) or SB203580 (n = 7) microinfusions (icv) just prior to U50. U50 significantly reduced extinction responding on the first extinction session in both groups (**p < 0.01 active lever, compared to U50-HC), regardless of p38 MAPK inhibition. There were no differences over subsequent extinction sessions. Rats underwent a cue-induced reinstatement test (2 weeks post-treatment), and prior treatment with SB + U50 on the first extinction session prevented U50’s long-lasting therapeutic reduction in cocaine seeking (**p < 0.01 active lever, comparing VEH + U50 to SB + U50; #p < 0.05 active lever, comparing U50-HC to VEH + U50)
