The cortical DA and NA systems are involved in the stress response. Long-term treatment with the SSRI, citalopram, affects the DA and NA systems, which may affect the therapeutic action of antidepressants.
A recent study measured the effects of long-term treatment with citalopram on DA and NA system responses in the rat prefrontal cortex (PFC) to acute handling stress using in vivo microdialysis. Acute stress increased DA and NA levels in the PFC.
These DA and NA responses were abolished by local infusion of a 5-HT1A receptor agonist, 8-OH-DPAT, into the PFC. The DA response was abolished by long-term treatment with citalopram, and the abolished DA response was reversed by local infusion of a 5-HT1A receptor antagonist, WAY-100,635, into the FPC. On the other hand, long-term treatment with citalopram reduced basal NA levels (to ~40% of controls), but not basal DA levels. NA response was not altered despite the small basal levels of NA.
These results show that the effects of chronic citalopram on the DA and NA systems are mediated by upregulation of the 5-HT1A receptor and expand our understanding of the mechanism of serotonergic antidepressants.