title: Schedule-controlled behavioral effects of the selective 2-amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic acid antagonist LY293558 in pigeons.
abstract: Behavioral effects of the selective 2-amino-3-(5-methyl-3-hydroxyisoxazol-4- yl)propanoic acid (AMPA) antagonist LY293558, along with its racemate (LY215490) and opposing enantiomer (LY293559) were evaluated in pigeons. When responding was maintained under a multiple fixed ratio 50 responses, fixed interval 5 minute (FRFI) schedule of food presentation, LY215490 completely antagonized the rate suppression induced by AMPA (10 mg/kg) and by the AMPA analog, 2-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionic acid (ATPA; 40 mg/kg) at 1.25 and 2.5 mg/kg, respectively. In contrast, LY215490, up to 10 mg/kg, was unable to antagonize the rate suppression induced by N-methyl-D-aspartic acid. LY293558, at 0.32 mg/kg, completely blocked the rate suppression produced by AMPA in both components of the multiple schedule. Similarly, LY293558, at 0.64 mg/kg, blocked the rate suppression induced by ATPA in both components. In contrast, the opposing enantiomer, LY293559, up to 10 mg/kg, was without effect on rate suppression produced by AMPA in this model. In additional studies, behavior was maintained under a schedule in which responding was maintained by food presentation in the presence of one key color and in the presence of a second key color, responding was maintained by food and simultaneously suppressed by electric shock ("punished responding"). LY215490 significantly increased punished responding at 10 and 30 mg/kg, whereas unpunished responding was unaffected until 56 mg/kg depressed it. LY293558 significantly increased punished responding at 3 mg/kg without having an effect on unpunished responding. LY293559, on the other hand, was unable to significantly increase punished responding at doses up to 175 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Benvenga
authors.forename: P L
authors.initials: PL
authors.lastname: Ornstein
authors.forename: J D
authors.initials: JD
authors.lastname: Leander
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D010856:Columbidae; D004597:Electroshock; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D013237:Stereoisomerism; D013777:Tetrazoles / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D007555:Isoxazoles; D011422:Propionates; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; D016202:N-Methylaspartate; C082309:tezampanel; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid