Behavioral Approaches to the Functional Assessment of NMDA-Mediated Neural Transmission in Intact Mice

摘要: Altered neurotransmission mediated by L-glutamate at the level of N-methyl-D-aspartic acid (NMDA) receptor complex has been implicated in pathophysiologic mechanisms several major neuropsychiatric disorders. Moreover, strategies for pharmacologic manipulation NMDA-mediated neural transmission have discussed treatment disorders as diverse schizophrenia, seizures, stroke, and traumatic brain injury, MK-801, an uncompetitive allosteric antagonist NMDA complex, was shown to antagonize electrically precipitated seizures a dose-dependent manner elicit popping behavior mice. Changes ability MK-801 or caused stress manipulations may reflect alterations populations NMDA-associated channels responsible these behavioral actions (e.g., number them open configuration their size, shape, charge characteristics). We used paradigms study glycinergic intervention (i.e., milacemide), inhibitors "nitric oxide cascade" 7-nitroindazole methylene blue), conventional haloperidol) atypical clozapine) antipsychotic medications on intact mouse. Also, marked differences inbred mouse strains suggest that they differ complexes mediating this behavior. This latter observation could lend itself identification specific genetic loci contributing In view phencyclidine (PCP) precipitate schizophreniform psychosis action it shares with neurotransmission, characterization mice inform search human susceptibility "PCP-psychosis" schizophrenia.