Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior. Study 2--The effects on behavior of block of NMDA receptors prior to injection of FG-7142.
The hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate initiation of lasting behavioral changes induced by the anxiogenic beta-carboline, FG-7142, was supported in this study. Behavioral changes normally induced by FG-7142 were blocked when the competitive NMDA receptor blocker, 7-amino-phosphono-heptanoic acid, was given prior to administration of FG-7142. When cats were subsequently given FG-7142 alone, the drug produced lasting behavioral changes like those reported previously. Flumazenil, a benzodiazepine receptor antagonist, reversed an increase in defensiveness produced by FG-7142 alone, replicating previous findings. The data are consistent with the hypothesis that NMDA-dependent long-term potentiation in limbic pathways subserving defensive response to threat mediates lasting increases in defensiveness produced by FG-7142.
Department of Psychology, Memorial University, St. John's, Newfoundland, Canada. radamec@morgan.ucs.mun.ca
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D002243:Carbolines / Q000494:pharmacology*; D002415:Cats; D004292:Dominance, Cerebral / Q000187:drug effects* / Q000502:physiology; D004525:Efferent Pathways / Q000187:drug effects / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D008032:Limbic System / Q000187:drug effects* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000503:physiopathology; D011235:Predatory Behavior / Q000187:drug effects / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology
D002243:Carbolines; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C035874:FG 7142; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid