Mk 801 hydrogen maleate

In general, all drugs were prepared fresh on the morning of the test session or the night before. Ethanol (95%) was diluted to 20% w/v in water for doses ≤ 1.0 g/kg, and to 25% and 30% for 1.5g/kg and 2.0g/kg tests respectively, leading to gavage volumes between 30–50ml for all doses tested. Pentobarbital was purchased in prepared form (Nembutal, 50 mg/ml), and midazolam hydrochloride (Sigma Aldrich) was diluted in saline to 3 mg/ml. Both drugs were administered through the nasogastric gavage, followed by a gavage of water up to the training dose volume (30–45ml). (+)-MK-801 hydrogen maleate (Sigma Aldrich) was diluted in saline to 0.2–0.5 mg/ml, morphine maleate salt (Sigma Aldrich) was diluted in saline to 5 mg/ml, and muscimol (Tocris) was diluted in saline to 7 mg/ml. Drug concentrations were based on the salt form of the drug. All i.m. drug preparations were less than 3ml, and if the injection volume exceeded 1ml, it was given across two injection sites. Vehicle injections matched the maximum drug volume given. All drugs administered i.m. (pentobarbital, MK-801, morphine, muscimol) were filtered through a 20μm millipore filter into a sterile vial prior to administration.

(±)-SKF-38393 hydrochloride, (±)-SCH-23390 hydrochloride, (-)-quinpirole hydrochloride, S-(-)-eticlopride hydrochloride, (+)-MK-801 hydrogen maleate, D(-)-2-amino-5-phosphonopentanoic acid (AP-5), and 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt hydrate (CNQX) were purchased from Sigma Aldrich (St. Louis, MO). Ifenprodil hemitartrate was purchased from Tocris Bioscience (Ellisville, MO). Each drug was prepared in sterile 0.9% NaCl (saline), except for ifenprodil, which was prepared in sterile water. Concentrations were calculated based on salt weight.

Drugs were administered s.c. in the midscapular region of the back in volumes of less than 3 ml. The doses (mg/kg) of current test drugs were expressed as the weight of the base and salt, except for nicotine and pentolinium, which were expressed as the weight of the base. Nicotine hydrogen tartrate salt, atropine, hexamethonium bromide, 1,2,2,6,6-pentamethylpiperidine (pempidine), pentolinium tartrate, chlorisondamine diiodide, phencyclidine hydrochloride, (+)-MK-801 hydrogen maleate (Sigma-Aldrich; St. Louis, MO), mecamylamine hydrochloride (Waterstone Technology; Carmel, IN), bupropion hydrochloride, varenicline dihydrochloride (Research Triangle Institute, Research Triangle Park, NC), cytisine (Atomole Scientific, Hubei, China), and dihydro-beta-erythroidine hydrobromide (Tocris Bioscience; Bristol, United Kingdom) were dissolved in physiological saline. Ketamine (Butler Animal Health Supply, Dublin, OH) and midazolam (5 mg/ml in physiologic saline; Bedford Laboratories; Bedford, OH) were obtained in solution. The pH of all solutions was adjusted to 7.

D-amphetamine sulfate and (+)-MK-801 hydrogen maleate (Sigma, St. Louis, MO) were prepared in sterile 0.9% NaCl (saline) and injected in a volume of 1 ml/kg. All injections were delivered subcutaneously (s.c.). The doses were calculated based on salt weight.

Cocaine-HCl, (+)-MK-801 hydrogen maleate, and memantine-HCl were purchased from Sigma-Aldrich (St. Louis, Missouri, USA) and dissolved in saline (0.9% NaCl). For training, Cocaine-HCl was dissolved to a final concentration of 12 mg/ml (of the salt) and administered in a volume of 1 ml/kg body weight. MK-801 and memantine (0.2 and 10 mg/kg, respectively; doses as free-base) and 0.9% saline were given at 2 ml/kg body weight. All drug treatments and saline were administered intraperitoneally (i.p.). The two NMDA receptor antagonists were used to ensure that any effects were due to common actions on this receptor system. Both MK-801 and memantine function as open-channel antagonists that block NMDA receptors only when these channels are activated (Chen et al. 1992 (link)). However, MK-801 and memantine interact with the NMDA receptor complex in distinct ways. Memantine is a low-affinity blocker with rapid blocking kinetics (Ribeiro Do Couto et al. 2004 ; Tzschentke and Schmidt 1999 (link)), while MK-801 is a high-affinity blocker with slower kinetics (Parsons et al. 1999 (link)). Additionally, these compounds differ in their binding site. MK-801 binds to the PCP site inside the pore of the receptor (Moring et al. 1994 (link); Sakurada et al. 1993 (link)), whereas memantine is believed to bind at or near the Mg2+ binding site (Chen and Lipton 1997 (link); Chen et al. 1992 (link)).