(A) Schematic of experimental paradigm for cocaine sensitization. Mice were exposed to cocaine (i.p., 20 mg/kg) or saline, either acutely, repeatedly or re-exposed following abstinence (challenge), with transcriptional dynamics studied at 0, 1, 2 or 4 hr. (B) Locomotor activity of mice following acute, repeated or challenge cocaine experiences (compared to saline). Sample size: acute and repeated saline n = 4; acute cocaine n = 30; repeated cocaine n = 22; challenge cocaine n = 19 mice. Results indicate mean ± s.e.m. (C) Expression matrix of IEG induction dynamics following cocaine experiences. Individual animals are represented in columns sorted according to time points of cocaine experiences [sample numbers per time point - LCtx: limbic cortex (n = 5–11), NAc: nucleus accumbens (n = 5–12), DS: dorsal striatum (n = 5–12), Amy: amygdala (n = 3–4), LH: lateral hypothalamus (n = 2–4), Hipp: hippocampus (n = 2–4)]. Fold induction is graded from blue (low) to red (high). Genes represented were induced at least 2-fold over control in any one of the brain regions studied. Genes were sorted according to peak induction in the DS. (D) Schematic of experimental paradigm for LiCl exposure. Mice were exposed to LiCl (i.p.) or saline, either acutely (150 or 250 mg/kg) or repeatedly (150 mg/kg). (E) Locomotor activity of mice following acute or repeated LiCl exposure (as in panel C). Sample size: n = 4–5. (F) Expression matrix of IEG induction dynamics following LiCl experiences (n = 4–5). Genes were sorted according to peak induction in the Amy. (G) Venn diagram indicating the identity of the most robustly induced genes common to cocaine and LiCl experiences (most appearances and lowest variance). (H) Confusion matrix representing the classification accuracy of decoding the recent experience (acute, chronic and challenge cocaine, acute and repeated LiCl and acute and repeated saline) of individual mice based on expression of Arc, Egr2, Egr4, Fos and Fosb induction in the LCtx, NAc, DS, Amy and LH using a KNN classifier. Accuracy is scaled from blue to green, with bright green corresponding to 100% accuracy (n = 37 mice). Overall accuracy = 97.3%. (I) Results of a permutation test for verifying classification. A randomization test was performed, in which the classifier was run on 105 random permutations of the association of individual mice to the appropriate experience, and the frequency of classification accuracies is plotted in grey, while the red dotted line represents the classification accuracy obtained for non-randomized data (97.3%).