NOREPINEPHRINE-INDEPENDENT REGULATION OF GRII MESSENGER-RNA IN-VIVO BY A TRICYCLIC ANTIDEPRESSANT

Desipramine (DMI), a tricyclic antidepressant drug used in the treatme nt of depression, has been shown to increase steady-state levels of gl ucocorticoid receptor type II (GRII) mRNA in vitro and in vivo. To det ermine whether this effect is secondary to norepinephrine (NE) reuptak e inhibition i.e., increases in synaptic NE induced by DMI, GRII mRNA levels were assayed in rat hippocampus following neurotoxic lesioning of NE neurons with DSP4. Chronic DMI treatment significantly increased GRII mRNA levels to the same degree in lesioned and non-lesioned anim als. In contrast to DMI, the non-tricyclic antidepressant fluoxetine h ad no effect on GRII mRNA. These results provide evidence which demons trates that a tricyclic antidepressant can regulate steady-state mRNA levels in vivo by a mechanism which is independent of its effects on s ynaptic monoamine levels.