Chronic antidepressant treatments decrease pro-opiomelanocortin mRNA expression in the pituitary gland: Effects of acute stress and 5-HT1A receptor activation

Consistent findings in depressed patients are hyperactivity in the hypothal amic-pituitary-adrenal (HPA) axis with high plasma concentrations of adreno corticotropic hormone and cortisol. Long-term antidepressant treatments see m to normalize this hyperactivity, suggesting a link between the HPA axis a nd the action of antidepressant treatments. The present study was carried o ut to study the effects of antidepressant treatments on pro-opiomelanocorti n (POMC) mRNA expression, with a focus on interaction with acute stress and 5-HT1A receptor activation. Male rats were treated for 21 days with saline , citalopram, fluoxetine, moclobemide or desipramine, and the expression of POMC mRNA in the anterior pituitary was analysed by semi-quantitative in s itu hybridization. All antidepressants, but not saline, cocaine and haloper idol, reduced POMC mRNA expression. The decrease in POMC mRNA was not obser ved until 9 days of citalopram treatment. Decreased POMC mRNA levels were a lso observed after 14 days of repeated electroconvulsive stimulation, The d ecreased POMC mRNA levels did not affect the stress-induced POMC mRNA incre ase, measured following swim stress and restraint stress. Finally, using Fo s as a marker for neural activity, we showed attenuation of 8-OH-DPAT-stimu lated activity in the paraventricular nucleus following 21 days of citalopr am treatment. In conclusion, antidepressant treatments decrease basal POMC mRNA expression without affecting the acute stress response, and the reduce d POMC mRNA may be related to reduced 5-HT1A-stimulated hypothalamic output .