Behavioral effects of NMDA receptor agonists and antagonists in combination with nitric oxide-related compounds.
Responding of rats was maintained under a 120-response fixed ratio (FR) schedule of food delivery, and animals received individual and combined injections of N-methyl-D-aspartic acid (NMDA), phencyclidine hydrochloride, (+)-MK-801 hydrogen maleate (MK-801), (+/-)-2-amino-5-phosphonopentanoic acid (AP5), 7-chlorokynurenic acid (7CK), ifenprodil tartrate, N(G)-nitro-L-arginine methyl ester hydorchloride (L-NAME), 7-nitroindazole, aminoguanidine hemisulfate, L-arginine, molsidomine, sodium nitroprusside, and 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8). Behavioral suppression after NMDA was completely and dose-dependently reversed by MK-801, phencyclidine, AP5, and aminoguanidine; partially and dose-dependently attenuated by molsidomine, ifenprodil, and 7CK; and not attenuated at all by L-NAME, 7-nitroindazole, or TMB-8. These findings suggested that behavioral suppression after NMDA was associated with nitric oxide from the inducible synthase. In a second series of experiments, comparable behavioral suppression by 0.1 mg/kg MK-801, but not 3 mg/kg phencyclidine, was attenuated by nitroprusside, molsidomine, and L-arginine, suggesting that suppressions from MK-801 and phencyclidine were mediated by different final common pathways, and that behavioral suppression from MK-801, but not phencyclidine, may be associated with Ca(2+)-dependent nitric oxide.
Smith
James B
JB
School of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA. jbsmith@mindspring.com
Ogonowski
Alison A
AA
D015763:2-Amino-5-phosphonovalerate / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000493:pharmacokinetics; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006146:Guanidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D007191:Indazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008981:Molsidomine / Q000008:administration & dosage / Q000493:pharmacokinetics; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000493:pharmacokinetics; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019001:Nitric Oxide Synthase / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000008:administration & dosage / Q000493:pharmacokinetics; D010622:Phencyclidine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000187:drug effects
D004338:Drug Combinations; D006146:Guanidines; D007191:Indazoles; D020030:Nitric Oxide Donors; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D007736:Kynurenic Acid; D010622:Phencyclidine; C010739:ifenprodil; C057013:7-chlorokynurenic acid; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester