PMID- 18761333
OWN - NLM
STAT- MEDLINE
DCOM- 20090209
LR  - 20131121
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1238
DP  - 2008 Oct 31
TI  - Differential effects of imipramine and phenelzine on corticosteroid receptor gene 
      expression in mouse brain: potential relevance to antidepressant response.
PG  - 93-107
LID - 10.1016/j.brainres.2008.08.018 [doi]
AB  - Although glucocorticoid feedback sensitivity of the 
      hypothalamic-pituitary-adrenal (HPA) axis is frequently impaired in depression, 
      atypical depression may exhibit increased feedback sensitivity. Because monoamine 
      oxidase inhibitors (MAOI) are often more effective than tricyclic antidepressants 
      (TCA) for atypical depression, we hypothesized that to normalize HPA function in 
      atypical depression, MAOI would differ from TCA in decreasing rather than 
      increasing feedback sensitivity. Consistent with this hypothesis and prior 
      evidence for opposing effects on HPA feedback in mice, we report contrasting 
      effects of chronic MAOI (phenelzine) and TCA (imipramine) treatment on neural 
      corticosteroid receptor gene expression in adrenalectomized male C57BL/6 mice 
      with fixed glucocorticoid levels. Our findings corroborate prior reports of 
      antidepressant-induced increases in hippocampal mineralocorticoid (MR) and 
      glucocorticoid receptor (GR) expression. However, hippocampal effects were 
      neither sustained nor representative of effects in other brain regions. 
      Imipramine typically increased and phenelzine decreased GR expression in other 
      feedback-related brain regions such as the paraventricular hypothalamus and 
      prefrontal cortex. Imipramine effects were limited to feedback-related regions, 
      whereas phenelzine had additional effects to decrease accumbens GR and central 
      amygdala MR expression. Our results suggest an expansion of the corticosteroid 
      receptor hypothesis of depression to include drug- and brain region-specific 
      actions of antidepressants to decrease as well as increase corticosteroid 
      receptor expression and feedback sensitivity. Our findings further suggest how 
      antidepressants could improve glucocorticoid regulation of HPA activity without 
      also facilitating the adverse effects of glucocorticoids on mood.
FAU - Heydendael, Willem
AU  - Heydendael W
AD  - Center for Neuropharmacology and Neuroscience, Albany Medical College, Mail Code 
      136, Albany, NY 12208, USA.
FAU - Jacobson, Lauren
AU  - Jacobson L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080816
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Receptors, Steroid)
RN  - O408N561GF (Phenelzine)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Adrenalectomy
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/*pharmacology
MH  - Brain/*drug effects/metabolism
MH  - Gene Expression/drug effects
MH  - Hypothalamo-Hypophyseal System/drug effects/physiology
MH  - Image Processing, Computer-Assisted
MH  - Imipramine/*pharmacology
MH  - In Situ Hybridization
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monoamine Oxidase Inhibitors/*pharmacology
MH  - Phenelzine/*pharmacology
MH  - Pituitary-Adrenal System/drug effects/physiology
MH  - Receptors, Steroid/biosynthesis/*drug effects
EDAT- 2008/09/02 09:00
MHDA- 2009/02/10 09:00
CRDT- 2008/09/02 09:00
PHST- 2008/05/29 00:00 [received]
PHST- 2008/08/07 00:00 [revised]
PHST- 2008/08/10 00:00 [accepted]
PHST- 2008/09/02 09:00 [pubmed]
PHST- 2009/02/10 09:00 [medline]
PHST- 2008/09/02 09:00 [entrez]
AID - S0006-8993(08)01995-1 [pii]
AID - 10.1016/j.brainres.2008.08.018 [doi]
PST - ppublish
SO  - Brain Res. 2008 Oct 31;1238:93-107. doi: 10.1016/j.brainres.2008.08.018. Epub 
      2008 Aug 16.