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Título: Monoamine oxidases and aggressive behaviour : clinical studies and animal models
Autores: Mejia, Jose.
Fecha: 2002
Publicador: McGill University - MCGILL
Fuente:
Tipo: Electronic Thesis or Dissertation
Tema: Monoamine oxidase.
Aggressiveness.
Aggressive behavior in animals.
Descripción: Monoamine oxidases (MAOs) are phylogenetically old enzymes which catalyze the deamination of monoamines. Interest in a relationship between MAO and aggressive behaviour derives from the report of a single family with a mutation which obliterates the activity of MAO A, as well as a long history of studies which substantiate a relationship between MAO activity and impulsive aggressive behaviour. The goals of this thesis were: (1) to examine the generalizability of the specific MAO mutation noted above; (2) to evaluate the relationship between platelet MAO activity and genetic polymorphisms in MAO genes, and (3) to extend knowledge regarding the developmental behavioural impact of MAO deficiency in mice treated pre- and perinatally with inhibitors of MAO.
In the first study we genotyped the C936T mutation in 100 subjects followed longitudinally and oversampled for aggressive behaviour. None of the subjects in our sample carried this mutation.
In the second study, we report the lack of association between platelet MAO activity and four intronic microsatellite polymorphisms of the MAO genes.
Studies of MAO knockout mice are at significant variance with clinical pharmacological experience using MAO inhibitors. Prompted by this and by other seminal basic experiments, we hypothesized that inhibition of MAO activity during the developmental period would have profound behavioural effects. MAO A and B inhibitors were administered, separately or in combination, to mice during gestation and lactation. Total prenatal MAO inhibition produced a severe pattern of behaviour, while MAO-B inhibited mice demonstrated a similar pattern with lower intensity. Aggression was elevated in MAO-A inhibited mice only after acute pharmacological challenges suggesting prenatal sensitization. Thus developmental inhibition of MAO activity engenders behavioural effects which parallel those observed in animals devoid functional MAO. These data underscore the importance of neurochemical changes during development and provide a possible model for uninhibited aggression, common in clinical populations.
Idioma: en