Figure 1.

Prolonged drug use produces low- and high-risk addiction phenotypes. A, Illustration of the experimental paradigm. Addiction risk screening occurred following 37 sessions of cocaine self-administration and included tests for loss of control over drug intake (Seeking), high motivation to obtain drug (Progressive ratio, PR) and drug use despite negative consequences (drug infusions paired with foot shock, Punish). Each test was separated by three baseline (BL) sessions. B–E, Low- and high-risk addiction phenotypes showed a significant difference in the number of active responses made during no drug periods (B, data averaged across the last 3 training sessions, ***p=0.001 vs. low-risk addiction phenotype and C, ^##main effect of phenotype, p=0.004; ^###main effect of session, p<0.001.), in the breakpoint reached on a PR schedule of reinforcement (D, ***p=0.001 vs. low-risk addiction phenotype), and in the percent of baseline infusions earned when infusions were paired with foot shock (E, *p<0.05 vs. low-risk addiction phenotype.) F,G, Total infusions (F) and the number of infusions earned across training (G) did not differ between low- and high-risk addiction phenotypes. White bars/symbols represent the low-risk addiction phenotype and grey bars/symbols represent the high-risk addiction phenotype. Black dots represent data points of individual animals. N=12–15/group.