The monoamines serotonin (5HT), noradrenaline and dopamine have been implicated in the pathophysiology of psychiatric disorders, specially of major depression, and in the mechanisms of their pharmacological therapies. It is possible that neuronal remodeling can be influenced by changes in the expression or metabolism of these molecules. In this regard, we have recently obtained evidence of a role for 5HT in the modulation of structural plasticity after treatment with the antidepressant fluoxetine in the mPFC, the hippocampus and other cortical regions, as well as in the amygdala (Varea et al., 2007c; Varea et al., 2007b; Guirado et al., 2009; Guirado et al., 2012). Chronic treatment with fluoxetine affects the expression of PSA-NCAM and molecules related to general and inhibitory neurotransmission. Moreover, at least in the mPFC, these changes occur through the activation of 5HT3 receptors (Varea et al., 2007c).
Recent results from our lab also show that dopamine, acting through D2 receptors (D2R) can also modulate PSA-NCAM, synaptophysin and GAD67 expression (Castillo-Gomez et al., 2008). Interneurons expressing PSA-NCAM express D2R. 6OHDA-induced depletion of cortical dopaminergic terminals produces a significant reduction in PSA-NCAM, synaptophysin and GAD67 expression in all prefrontocortical regions. Similar results were obtained with chronic treatment with haloperidol (a D2R antagonist) and the opposite effects were found with a D2R agonist (PPHT), suggesting that the effects of dopamine on the expression of these molecules are mediated by D2R. Moreover, in an article published last year we demonstrate that the presence of PSA-NCAM is necessary for these changes in the expression of molecules related to general and inhibitory neurotransmission and that PSA-NCAM is an important regulator of perisomatic innervation on pyramidal neurons of the mPFC (Castillo-Gomez et al., 2011).