Chronic antidepressant treatments decrease pro-opiomelanocortin mRNA expression in the pituitary gland: effects of acute stress and 5-HT(1A) receptor activation.
Consistent findings in depressed patients are hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis with high plasma concentrations of adrenocorticotropic hormone and cortisol. Long-term antidepressant treatments seem to normalize this hyperactivity, suggesting a link between the HPA axis and the action of antidepressant treatments. The present study was carried out to study the effects of antidepressant treatments on pro-opiomelanocortin (POMC) mRNA expression, with a focus on interaction with acute stress and 5-HT(1A) 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 situ hybridization. All antidepressants, but not saline, cocaine and haloperidol, reduced POMC mRNA expression. The decrease in POMC mRNA was not observed until 9 days of citalopram treatment. Decreased POMC mRNA levels were also observed after 14 days of repeated electroconvulsive stimulation. The decreased POMC mRNA levels did not affect the stress-induced POMC mRNA increase, measured following swim stress and restraint stress. Finally, using Fos as a marker for neural activity, we showed attenuation of 8-OH-DPAT-stimulated activity in the paraventricular nucleus following 21 days of citalopram treatment. In conclusion, antidepressant treatments decrease basal POMC mRNA expression without affecting the acute stress response, and the reduced POMC mRNA may be related to reduced 5-HT(1A)-stimulated hypothalamic output.
Jensen
J B
JB
Department of Neurobiology, H. Lundbeck A/S, Copenhagen, Denmark. jbj@azign.com
Mørk
A
A
Mikkelsen
J D
JD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012149:Restraint, Physical; D012640:Seizures / Q000503:physiopathology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013315:Stress, Psychological / Q000378:metabolism*; D013550:Swimming / Q000523:psychology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000928:Antidepressive Agents; D015283:Citalopram; D011333:Pro-Opiomelanocortin; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors