N hexane dichloromethane diethylamine 75 25 0.1

R-ketamine hydrochloride and S-ketamine hydrochloride were prepared by recrystallization of RS-ketamine (Ketalar, ketamine hydrochloride, Daiichi Sankyo Pharmaceutical, Tokyo, Japan) and d-(−)-tartaric acid (or l- (+)-tartaric acid), as described previously.³⁴ The purity of these stereoisomers was determined by a high-performance liquid chromatography (CHIRALPAK IA, column size: 250 × 4.6 mm, mobile phase: n-hexane/dichloromethane/diethylamine (75/25/0.1), Daicel, Tokyo, Japan). NBQX, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (catalog number: 0373, Tocris Bioscience, Bristol, UK, 10 mg kg⁻¹) was dissolved in saline. ANA-12, N2-(2-{[(2-oxoazepan-3-yl) amino]carbonyl}phenyl)benzo[b]thiophene-2-carboxamide (catalog number: BTB06525SC, Maybridge, Trevillett Tintagel, Cornwall, UK, 0.5 mg kg⁻¹) was prepared in vehicle of 1% dimethylsulfoxide in phosphate-buffered saline. The dose of ketamine, NBQX and ANA-12 was selected as reported previously.^{34 , 35 , 36 (link), 37 (link), 38 (link), 39 (link), 40 (link)} Other reagents were purchased commercially.

(R)-ketamine hydrochloride was prepared by recrystallization of (R,S)-ketamine (Ketalar^®, ketamine hydrochloride, Daiichi Sankyo Pharmaceutical Ltd., Tokyo, Japan) and D-(−)-tartaric acid, as described previously^{25 (link)}. The purity of (R)-ketamine was determined by a high-performance liquid chromatography (CHIRALPAK^® IA, Column size: 250 × 4.6 mm, Mobile phase: n-hexane/dichloromethane/diethylamine (75/25/0.1), Daicel Corporation, Tokyo, Japan). The dose (10 mg/kg as ketamine hydrochloride) of (R)-ketamine and lanicemine (AZD6765; Sigma-Aldrich Co. Ltd, St Louis, MO, USA) was used as previously reported^{26 (link)–30 (link),57 (link)}.