The role of VTA/RMTg projections to the lateral habenula (LHb) on ulnar inhibition of cocaine locomotion. (A) Ulnar MS increases LHb temperature (A1–3). (B) Activation of LHb neurons projecting to the VTA/RMTg regions following ulnar stimulation. The number of c-fos positive cells in the LHb increased by approximately 2-fold in ulnar MS rats (MS, B2-B3; n = 5) compared to rats in the control group (Con; B1; n = 5). (C) c-fos LHb positive cells (C2) were labeled retrogradely with fluorogold (FG; yellow; C1) injected into the VTA/RMTg regions (C1–3). The number of c-fos positive cells double-labeled with FG significantly increased in ulnar MS (n = 5), compared to control (Con; n = 5; C4). # p < 0.05 vs. Con. (D) Electrolytic lesions of LHb (LHb X; D1–2) prevented ulnar MS-induced inhibition of cocaine-induced locomotion (LHb X + MS; n = 5), compared to the control groups of LHb lesion only (n = 5) and Sham + MS (n = 5) (D3). # p < 0.05 vs. LHb X. *p < 0.05 vs. Sham + MS.