Noradrenergic

The major mammalian enzymes involved in catecholamine metabolism are monoamine oxidase (MAO) and catechol O-methyl transferase (COMT). Mice lacking MAO-A have increased levels of NE and 5HT in the brain.26 Behavioral evaluation of these animals showed a reduction in anxiety-related behaviors in the open field, but it remains unclear whether this effect is anxiety specific or related to a general alteration in sensory ability in the animals. MAO-B mutants exhibit an increase in brain and urinary b-phenylethylamine (the preferential MAO-B substrate), with no alterations in brain levels of NE, 5HT, or DA. The MAO-B mutants did not exhibit any behavioral differences in anxiety tests such as the open field or EPM. Deletion of the gene for COMT produced an increase in dopamine in the frontal cortex of male, but not female, mutant mice, and no change in NE or 5HT levels in any region.28 When tested behaviorally, only female COMT mutants exhibited anxiogenic (increased anxiety) behavior in the light/dark box test.

Reuptake of NE via the norepinephrine transporter (NET) is a major means of inactivation of the released transmitter in the brain and peripheral nervous system.29 Deletion of the NET gene results in a sixfold decrease in the clearance rate for NET and a twofold increase in the extracellular NE levels.30 NET-deficient mice exhibited reduced anxiety-like behavior in the open field test, but this is difficult to interpret given the overall difference in basal activity levels in the mutant versus wild-type mice.30

Deletion of the a2-adrenoceptor resulted in an anxiogenic phenotype in the EPM and open field tests.31 This is thought to be related to the increased NE turnover and synaptic concentrations of NE found in the mutant mice.

Getting to Know Anxiety

Getting to Know Anxiety

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