title: NMDA receptor antagonists block development of tolerance to m-CPP-induced increases in ACTH concentrations in rats.
abstract: We have recently demonstrated that a single administration of m-chlorophenylpiperazine (m-CPP, a preferential 5-HT2C receptor agonist) produces tolerance to its stimulatory effect on adrenocorticotropic hormone (ACTH) concentrations when challenged 24 h later with the same dose of m-CPP. In the present study, we studied the effects of pretreatment with various N-methyl-D-aspartate (NMDA) receptor antagonists on development of tolerance to m-CPP's stimulatory effect on ACTH concentrations. Pretreatment with various NMDA receptor antagonists such as 5.7-dichlorokynurenic acid (1.0 mg/kg), 3-amino-1-hydroxy 2-pyrrolidone (1.0 mg/kg), dizocilpine (0.1 mg/kg) and ifenprodil (1.0 mg/kg) injected 30 min before the first injection of m-CPP (2.5 mg/kg) blocked development of tolerance to m-CPP's stimulatory effect on ACTH concentrations in rats injected 24 h later with the same dose (2.5 mg/kg) of m-CPP. These findings suggest that tolerance to postsynaptic 5-HT2C receptor-mediated response is initiated though stimulation of NMDA receptor complex and, furthermore, demonstrate a functional interaction between the 5-HT and glutamate systems.
authors.affiliation: Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892-1264, USA. pas09@helix.nih.gov
authors.forename: P
authors.initials: P
authors.lastname: Mazzola-Pomietto
authors.forename: C S
authors.initials: CS
authors.lastname: Aulakh
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004361:Drug Tolerance; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D010880:Piperidines; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D016291:Dizocilpine Maleate; D000324:Adrenocorticotropic Hormone; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; D010622:Phencyclidine; C010739:ifenprodil; C015068:1-(3-chlorophenyl)piperazine; C066192:5,7-dichlorokynurenic acid; D004121:Dimethyl Sulfoxide