To evaluate the role of the DC somatosensory pathway in ulnar MS-induced inhibition of cocaine locomotion, bilateral lesions of the DC were made at the C3 level 7–10 days before testing (Fig. 2A1 and A2). Inhibition of cocaine locomotion by ulnar MS was prevented by DC lesions (the term ‘X’ refers to ‘lesion’; two-way ANOVA: group factor F = 4.095, p = 0.050; time factor F = 6.202, p < 0.001; interaction F = 0.603, p = 0.804; Fig. 2A3), or by bilateral lesions of the CN, the second-order neurons in the DC pathway (p < 0.05, CN X + MS vs. Sham + MS, Fig. 2B1–3). Taken together, these results indicate that the DC pathway mediates ulnar MS-induced inhibition of cocaine locomotion.Figure 2The role of the dorsal column somatosensory pathway in ulnar nerve inhibition of cocaine-induced locomotion. (A) Dorsal column lesions (DC X) were introduced bilaterally at the C3 level of the spinal cord (A1), as shown in a representative image of toluidine blue staining (A2). Mechanical stimulation (MS) of the ulnar site (MS) reduced cocaine-induced locomotion (Sham + MS; n = 10), compared to the control group (DC X; n = 6), which was blocked by surgical lesion of DC prior to MS (DC X + MS; n = 7; A3). *p < 0.05 vs. Sham + MS. (B) When CN lesions (CN X) were performed bilaterally 7–10 days prior to the experiment (B1 and B2), MS of the ulnar site failed to reduce cocaine locomotion (CN X + MS; n = 10), compared to the control groups of CN X (CN X; n = 5), Sham (n = 5) and Sham + MS (n = 5; B3). *p < 0.05 vs. CN X + MS. (C) Representative waveforms and peri-stimulus time histograms of in vivo extracellular recordings in CN neurons (C1–2). Ulnar MS markedly increased CN WDR (n = 6) and LT (n = 7) spiking activity (C3). *p < 0.05 vs. Baseline. (D) Increased expression of c-fos immunopositive cells following ulnar stimulation (MS, n = 6; D1 & D3) in the dorsomedial portion of the CN (D2), compared to the control group (Con, n = 6; D1). Bar = 20 µm. *p < 0.05 vs. Con (D3). Figure 3The effects of STT or VPL lesions on the ulnar inhibition of cocaine locomotion. (A) STT lesions (STT X) at the C3 level of the spinal cord (A1–2) did not affect ulnar MS-induced inhibition of cocaine-induced locomotion (STT X + MS; n = 8) when compared to the control group (STT X; n = 7) or ulnar stimulation without STT lesion (Sham + MS; n = 6; A3). *p < 0.05 vs. STT X. Representative images of STT lesions stained by toluidine blue (A2). (B) Bilateral chemical lesions of the VPL (B1–2) block the inhibitory effects of cocaine locomotion by ulnar MS (VPL X + MS; n = 7), compared to the control groups of VPL X (n = 7) and Sham + MS (n = 6; B3). *p < 0.05 vs. Sham + MS or VPL X + MS.