Effect of Monoamine Oxidase Gene Knockout on Dopamine Metabolism in Mouse Brain Structures

Abstract

Experiments were performed on knockout Tg8 mice lacking monoamine oxidase A gene that plays a major role in dopamine catabolism. The study by the method of high-performance liquid chromatography revealed considerable regional differences in the contents of dopamine and its metabolite dihydroxyphenylacetic acid in brain structures of these animals. Tg8 mice differed from the parent C3H/HeJ strain by low level of dihydroxyphenylacetic acid in the striatum, midbrain, hypothalamus, and hippocampus and high concentration of dopamine in the striatum. No differences were revealed in the contents of dopamine and dihydroxyphenylacetic acid in the frontal cortex and amygdala. The 2.4-4.8-fold decrease in the content of dihydroxyphenylacetic acid in various brain structures was not accompanied by changes in dopamine concentration. These data reflect the effective compensation for deficiency of dopamine metabolism. Our results suggest that monoamine oxidases A and B and catechol-O-methyltransferase play different roles in dopamine metabolism in various brain structures.

Mesocorticolimbic monoamine correlates of methamphetamine sensitization and motivation

“…The fact that the rise in DA EC elicited by the MA challenge injection was more persistent in MA-experienced vs. acutely treated animals (Figure 1) suggests that perhaps repeated drug experience lowered DA catabolism. As mentioned above, MA inhibits MAO (Fleckenstein et al, 2007) and the possibility exists that with repeated drug experience, this mechanism may contribute to this drug's capacity to promote higher DA EC levels, particularly within the NAC (Popova et al, 2004). In contrast to striatum, frontal cortical structures exhibit low DAT expression (Sesack et al, 1998).…”

Hypothalamic Galanin‐Like Peptide Rescues the Onset of Puberty in Food‐Restricted Weanling Rats

“…Recently, our laboratory reported that GALP knockout mice developed normally with an onset of puberty similar to that of normal littermates (51). Numerous studies have demonstrated a lack of particular phenotypes in knockout mice as a result of hypothalamic compensatory mechanisms (52–57). Clearly, other hypothalamic systems are implicated in regulating the timing of the onset of puberty (58) and even mediating the effects of leptin to modulate the timing of the onset of puberty (59–61).…”

Effect of Monoamine Oxidease A Knockout on the Expression of 5-HT1A Receptors

“…However, we recently found significant regional specificity of the effect of MAO A knockout on the metabolism of serotonin and catecholamines in different brain structures. The frontal cortex was more resistant to the absence of MAO A than others, including the hippocampus, midbrain, hypothalamus, striatum and amygdala [2,10].…”

“…Recently, a strain of transgenic mice (Tg8) with an irreversibly destroyed gene of MAO A was obtained at Curie Institute [1]. Tg8 mice are deprived of MAO A and characterized by high levels of serotonin and noradrenalin and low concentrations of the final products of the oxidative deamination of serotonin and dopamine, 5-hydroxyindolacetic (5-HIAA) and 3,4-dihydroxyphenylacetic (DOPAA) acids [1,2]. In this work, we studied the effect of the genetic knockout of MAO A on the functional state and level of the mRNA of 5-çí 1Ä receptors in brain structures.…”

“…However, we recently found significant regional specificity of the effect of MAO A knockout on the metabolism of serotonin and catecholamines in different brain structures. The frontal cortex was more resistant to the absence of MAO A than others, including the hippocampus, midbrain, hypothalamus, striatum and amygdala [2,10].The purpose of this study was to investigate effect of the genetic knockout of MAO A on the functional state of 5-çí 1Ä receptors and the expression of the mRNA of 5-çí 1Ä receptors in brain structures.Experiments were carried out with pubertal Tg8 mice; C3H/HeJ (C3H) mice obtained from Curie Institute (France) served as control. Mice weighed about 25 g and were maintained under the standard conditions in the vivarium of the Institute of Cytology and Genetics (Siberian Division, Russian Academy of Sciences).…”