Noradrenergic systems tricyclic antidepressant effects

Virtually all types of drug that have been shown to be effective in major depression exert profound effects on the functioning of the serotoninergic or noradrenergic systems, or both. Although some treatments have been shown to decrease the sensitivity of certain postsynaptic 5-HT and NE receptors, it is generally believed that it is an enhancement of neurotransmission in these systems that is responsible for the improvement of the core symptoms of depression. For instance, long-term administration of tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) decreases the density of (3-adrenoceptors and cortical 5-HT2 receptors (Blier and Abbott 2003). 

The tricyclic and other NE-active antidepressants do not block dopamine (DA) transport via DAT) they thereby differ from central nervous system (CNS) stimulants, including cocaine, methylphenidate, and amphetamines see Chapter 10). Nevertheless, they may indirectly facilitate effects of DA by inhibiting the nonspecific transport of DA into noradrenergic terminals in the cerebral cortex. Tricyclic antidepressants also can desensitize D antoreceptors through uncertain mechanisms and with uncertain behavioral contributions. 

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