PT  - JOURNAL ARTICLE
AU  - Stout, Steven C.
AU  - Owens, Michael J.
AU  - Nemeroff, Charles B.
TI  - Regulation of Corticotropin-Releasing Factor Neuronal Systems and Hypothalamic-Pituitary-Adrenal Axis Activity by Stress and Chronic Antidepressant Treatment
AID  - 10.1124/jpet.300.3.1085
DP  - 2002 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1085--1092
VI  - 300
IP  - 3
4099  - http://jpet.aspetjournals.org/content/300/3/1085.short
4100  - http://jpet.aspetjournals.org/content/300/3/1085.full
SO  - J Pharmacol Exp Ther2002 Mar 01; 300
AB  - In a series of experiments, we tested the hypothesis that chronic antidepressant drug administration reduces the synaptic availability of corticotropin-releasing factor (CRF) through one or more effects on CRF gene expression or peptide synthesis. We also determined whether effects of acute or chronic stress on CRF gene expression or peptide concentration are influenced by antidepressant drug treatment. Four-week treatment with venlafaxine, a dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor, and tranylcypromine, a monoamine oxidase inhibitor, resulted in an attenuation of acute stress-induced increases in CRF heteronuclear RNA (hnRNA) synthesis in the paraventricular nucleus (PVN). Trends toward the same effect were observed after treatment with the 5-HT reuptake inhibitor fluoxetine, or the NE reuptake inhibitor reboxetine. CRF mRNA accumulation in the PVN during exposure to chronic variable stress was attenuated by concurrent antidepressant administration. Basal CRF hnRNA and mRNA expression were not affected by antidepressant treatment in the PVN or in other brain regions examined. Chronic stress reduced CRF concentrations in the median eminence, but there were no consistent effects of antidepressant drug treatment on CRF, serum corticotropin, or corticosterone concentrations. CRF receptor expression and basal and stress-stimulated HPA axis activity were unchanged after antidepressant administration. These results suggest that chronic antidepressant administration diminishes the sensitivity of CRF neurons to stress rather than alters their basal activity. Additional studies are required to elucidate the functional consequences and mechanisms of this interaction. The American Society for Pharmacology and Experimental Therapeutics