Additional file 1: of Toll-like receptor 3 modulates the behavioral effects of cocaine in mice

Supplementary material for ORF of LV-TLR3. (DOCX 14 kb

Validation plots of the PLS models after application of OSC in striatum.

<p>(A) control vs. 20 mg/kg cocaine; (B) control vs. nicotine +2 mg/kg cocaine; (C) 2 mg/kg cocaine vs. nicotine +2 mg/kg cocaine; (D) control vs. nicotine; (E) control vs. 2 mg/kg cocaine.</p

Validation plots of the PLS models after application of OSC in NAc.

<p>(A) control vs. 20 mg/kg cocaine; (B) control vs. nicotine +2 mg/kg cocaine; (C) 2 mg/kg cocaine vs. nicotine +2 mg/kg cocaine; (D) control vs. 2 mg/kg cocaine.</p

600 MHz CPMG ¹HNMR spectra of the NAc from mice.

<p>(A) control; (B) 2 mg/kg cocaine; (C) 20 mg/kg cocaine; (D) nicotine; (E) nicotine +2 mg/kg cocaine.</p

Comparison of NAc from mice by applying PLS loading plots for the region 9.4–5.1 and 4.6-0.2 ppm (440 segments) after application of OSC data filter.

<p>(A) control vs. 20 mg/kg cocaine; (B) control vs. nicotine +2 mg/kg cocaine; (C) 2 mg/kg cocaine vs. nicotine +2 mg/kg cocaine;(D) control vs. 2 mg/kg cocaine.</p

Comparison of striatum from mice by applying PLS loading plots for the region 9.4–5.1 and 4.6-0.2 ppm (440 segments) after application of OSC data filter.

<p>(A) control vs. 20 mg/kg cocaine; (B) control vs. nicotine +2 mg/kg cocaine; (C) 2 mg/kg cocaine vs. nicotine +2 mg/kg cocaine; (D) control vs. nicotine; (E) control vs. 2 mg/kg cocaine.</p

Changed metabolites in brain NAc and altered metabolic pathways for the most relevant distinguishing metabolites with nicotine or cocaine treatment.

<p>(A) In the left, changed metabolites in 20 mg/kg cocaine group exhibit similar changes with combinational drugs group, sharing 10 overlapped metabolites. In the right, a part of modified metabolites showed considerable overlap between 20 mg/kg cocaine group and 2 mg/kg cocaine group or nicotine group. Among them, two shared metabolites between 2 mg/kg cocaine group and nicotine group are Glu and 1-methylhistidine; four shared metabolites between 2 mg/kg cocaine group and 20 mg/kg cocaine group are Gln, L-methionine, α-ketoglutaric acid and phosphocholine; four shared metabolites between nicotine group and 20 mg/kg cocaine group are tryptamine, Lac, Cre and proline. (B) Blue metabolites are upregulated, and red metabolites are downregulated.</p

OSC-PLS scores plots of NAc from mice.

<p>(A) control vs. 20 mg/kg cocaine; (B) control vs. nicotine +2 mg/kg cocaine; (C) 2 mg/kg cocaine vs. nicotine +2 mg/kg cocaine; (D) control vs. 2 mg/kg cocaine.</p

Box-and-whisker plots illustrate progressive changes of the metabolites among 5 treatment groups: saline (control), 2 mg/kg cocaine (II), nicotine (III), nicotine +2 mg/kg cocaine (IV) and 20 mg/kg cocaine (V).

<p>Horizontal line in the middle portion of the box, median; bottom and top boundaries of boxes, lower and upper quartile; whiskers, 5th and 95th percentiles; open circles, outliers.</p