Abstinence-induced escalation of nicotine intake is blocked by a CRF1 receptor antagonist. (A) Effect of a CRF1 antagonist (MPZP, s.c., −1 h) on nicotine self-administration during the active period in rats given extended access to nicotine (*, P < 0.05 vs. baseline; #, P < 0.05 vs. after-abstinence vehicle treatment, n = 8). (B) Correlation between magnitude of the nicotine-deprivation effect and percentage changes in the nicotine-deprivation effect after CRF1 antagonist. The higher the nicotine-deprivation effect, the more effectively the antagonist blocked self-administration of nicotine (r = −0.71, P < 0.05). The x axis represents active responses after vehicle injection, and the y axis represents the reduction in active responses after the highest dose of MPZP (20 mg/kg), in percentage changes compared with active responses after vehicle injection. (C) Lack of effect of the CRF1 receptor antagonist (MPZP, s.c., −1 h) on baseline nicotine self-administration responding in rats given limited access to nicotine (n = 10). Data represent mean ± SEM.