Mk 801 hydrogen maleate mk 801

TAK‐137 was synthesized by Takeda Pharmaceutical Company Limited (Fujisawa, Japan) and suspended in 0.5% (w/v) methylcellulose in distilled water; oral administration (p.o.) was conducted at a volume of 2 mL kg⁻¹ in rats, 20 mL kg⁻¹ in mice, and 5 mL kg⁻¹ in monkeys. A solution of 0.5% methylcellulose was administered as the vehicle control. Methamphetamine hydrochloride (METH, Sumitomo Dainippon Pharma, Osaka, Japan) at 0.5 mg kg⁻¹ and (+)‐MK‐801 hydrogen maleate (MK‐801, Sigma‐Aldrich St Louis, MO) at 0.08 or 0.1 mg kg⁻¹ were dissolved in 0.9% saline and subcutaneously administered (s.c.) to rats at a volume of 2 mL kg⁻¹. Phencyclidine hydrochloride (PCP, Sigma‐Aldrich, Poole, UK) (2 mg kg⁻¹) was dissolved in 0.9% saline and administered intraperitoneally (i.p.) to rats at a volume of 1 mL kg⁻¹ twice per day for 7 days. Ketamine hydrochloride (KETALAR^Ⓡ, Daiichi Sankyo Propharma Co. Ltd, Tokyo, Japan) was dissolved in 0.9% saline and administered intramuscularly (i.m.) to monkeys at a volume of 5 mL kg⁻¹.

We used three agonists of ionotropic glutamate receptors; N-methyl-D-asparatic acid (NMDA) (≥98%; Sigma-Aldrich, St. Louis, MO), (±)-α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), (≥98%; Sigma-Aldrich), and kainic acid n-hydrate (Kainate) (≥98%; Wako), and two antagonists; (+)-MK-801 hydrogen maleate (MK-801) (≥98%; Sigma-Aldrich) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt hydrate (NBQX) (≥98%; Sigma-Aldrich). Chemicals dissolved in water were stored as 10 mM stock solutions, and kept at 4°C until use. This stock solution was added to each 5 ml of breeding water containing one adult female (one-month old or older) at 30 h after ovulation in a 5-ml sampling tube (INA OPTICA, Osaka, Japan). A total of 15 individuals were used for these experiments. The concentrations of MF, agonists and antagonists used are as follows: MF (0.8 μM), MK-801 (20 μM), NBQX (100 and 200 μM), NMDA, AMPA and Kainate (100 μM). Differences between treatments were statistically analyzed by Fisher’s exact probability test with Holm’s correction using R 2.15.3 [48 ].

(+)-MK-801 hydrogen maleate (MK-801) was purchased from Sigma Aldrich (St. Louis, Missouri, United States), dissolved in non-chlorinated water, and was administered to zebrafish via water immersion for 3 h per day, for 7 consecutive days at 1,349 ng/mL (4μΜ). Τhe dose of MK-801 was chosen based on a previous study in zebrafish (Perdikaris and Dermon, 2022 (link)). Control animals were exposed to the same conditions but treated with drug-free vehicle. Immediately after the daily treatment the animals returned to their home tanks and 2–3 h later, fish were allowed to have access to food.
At the 8th day of the experimental procedure, 24 h after MK-801 administration, zebrafish were individually subjected to a battery of behavioral tests as described below and then were immersed in fresh solution of 5-bromo-2′-deoxyuridine (ΒrdU) (Sigma-Aldrich, Deisenhofen, Germany) (5 mM, diluted in tank water) for 5 h, to label active cycling cells (Makantasi and Dermon, 2014 (link)). Fish were then allowed to survive for 15 h (short-term/ST survival group) and an additional group of fish were allowed to survive for 14 days (long-term/LT survival group), following BrdU administration at Day 8. The densities and phenotypes of newborn BrdU+ cells were assessed at Day 9 and Day 22 of the experimental protocol (Figure 1A).