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Supporting Information

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Figure S1:Animal weight loss during chronic HER or METH treatment and withdrawal. The line graphs represent the weight of animals at three time-points: before the first injection (naive), 14 h after the last injection (chronic), and 12 days after the last injection (withdrawal) of METH (left), HER (middle) or SAL (right) using the diurnal (up) or nocturnal (down) treatment scheme. Single lines show single animals. Chronic diurnal treatment with both METH (P < 0.01) and HER (P < 0.05) caused a reduction in body weight. A more severe loss of body weight was observed following nocturnal chronic treatment with both METH (P < 0.001) and HER (P < 0.01).

Figure S2:Acquisition of locomotor sensitization to HER or METH after chronic treatment and withdrawal. The line graphs show the locomotor response to METH (2 mg/kg, left), HER (10 mg/kg, middle) or SAL (right) at three time-points. Responses to the first injection (Naive), 14 h after the last injection (Chronic), 12 days after the last injection (Withdrawal) using the diurnal (up) or nocturnal (down) treatment scheme are reported. Single lines show single animals.

Figure S3:Numbers of genes regulated by drug treatment. The Venn diagram represents numbers of probes significant for the main factors (drug, time) and interaction (Two-way ANOVA, FDR < 5%).

Figure S4:Dose-dependent effects of treatment on Hif3a gene and lack of the effect on Gm129 gene. Barplots show fold change of gene expression for every day of treatment and withdrawal in which the expression was measured. Scatterplots show dose effect on gene expression alteration of Hif3a (P < 0.05) and Gm129 (P > 0.05) genes.

Figure S5:Naloxone-precipitated withdrawal in mice following chronic treatment with METH or HER. Bar graphs summarising the mean and standard deviation of jumps in response to naloxone (s.c., 4 mg/kg) after the indicated treatment (n = 4–7). HER-treated mice exhibited significant withdrawal signs 14 h after the last injection (P < 0.05). METH-treated mice did not exhibit significant withdrawal signs 14 h after the last injection.

Table S1: Probes with uncorrected significance (P < 0.05).

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