a, Antidepressant response to systemic ketamine injection (25 mg kg–1, i.p.) in FST 1 h after treatment in cLH rats. n = 10, 8, 6 for wild-type rats injected with saline, cLH rats injected with saline, and cLH rats injected with ketamine, respectively. b, c, OFT of cLH rats after bilateral infusion of ketamine (25 μg, 1 μl each side) or mibefradil (10 nmol, 1 μl each side; b), AP5 (40 nmol, 1 μl each side) or NBQX (1 nmol, 1 μl each side; c) into the LHb. n = 7, 10, 6 rats (b) and 8, 9, 9 rats (c) for saline, ketamine and mibefradil, respectively. d, OFT of CRS mice 1 h after intraperitoneal injection of saline or ethosuximide. n = 6, 9 mice for saline and ethosuximide, respectively. e–g, Representative ion chromatograms of separation of ketamine including double blank (e), brain calibrator spiked with 100 ng ml–1 ketamine (KET) (f) and a habenular sample from a cLH rat bilaterally infused with 25 μg μl–1 ketamine into the LHb 1 h earlier (g). Fluvoxamine (FFSM) is used as the internal standard. Data are mean ± s.e.m.; *** P < 0.001, **** P < 0.0001; n.s., not significant. One-way ANOVA (a–c), two-tailed Mann–Whitney test and unpaired t-test (d).