PMID- 16382205
OWN - NLM
STAT- MEDLINE
DCOM- 20060721
LR  - 20200106
IS  - 1734-1140 (Print)
IS  - 1734-1140 (Linking)
VI  - 57
IP  - 6
DP  - 2005 Nov-Dec
TI  - Combined treatment with imipramine and metyrapone induces hippocampal and 
      cortical brain-derived neurotrophic factor gene expression in rats.
PG  - 840-4
AB  - The problem of drug-resistant depression indicates a strong need for alternative 
      antidepressant therapies. Recently it was shown that joint administration of 
      imipramine (IMI) and metyrapone (MET), an inhibitor of glucocorticoid synthesis, 
      produced a more potent "antidepressant" effect in the forced swimming test than 
      did treatment with either drug alone. Our studies also showed that 
      co-administration of IMI and MET to drug-resistant, unipolar depressed patients 
      effected a clinical improvement. In addition, recent studies indicated a role of 
      the brain-derived neurotrophic factor (BDNF) in the mechanism of action of 
      antidepressant drugs (ADs). Since the most potent effect of ADs on BDNF gene 
      expression was found after prolonged treatment, in the present research we 
      investigated the influence of repeated treatment with IMI (5 or 10 mg/kg) and MET 
      (50 mg/kg), given separately or jointly (twice daily for 14 day), on the BDNF 
      mRNA level (the Northern blot) in the hippocampus and cerebral cortex. The 
      experiment was carried out on male Wistar rats. The tissue for biochemical assays 
      was collected 24 h after the last dose of IMI and MET. The obtained results 
      showed that in the hippocampus IMI (10 mg/kg) and cerebral cortex IMI (5 mg/kg) 
      and MET (50 mg/kg) significantly elevated the BDNF mRNA level. Joint 
      administration of IMI (10 mg/kg) and MET (50 mg/kg) induced a more potent 
      increase BDNF gene expression in both the examined brain regions (compared to the 
      treatment with either drug alone). Moreover, the obtained results suggested that 
      BDNF may be involved in the mechanism of the synergistic antidepressant effect of 
      IMI and MET in drug-resistant depressed patients.
FAU - Rogoz, Zofia
AU  - Rogoz Z
AD  - Department of Pharmacology, Institute of Pharmacology, Polish Academy of 
      Sciences, Smetna 12, PL 31-343 Krakow, Poland. rogoz@if-pan.krakow.pl
FAU - Legutko, Beata
AU  - Legutko B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
RN  - OGG85SX4E4 (Imipramine)
RN  - ZS9KD92H6V (Metyrapone)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Enzyme Inhibitors/*pharmacology
MH  - *Gene Expression Regulation
MH  - Hippocampus/*drug effects/metabolism
MH  - Imipramine/*pharmacology
MH  - Male
MH  - Metyrapone/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Steroid 11-beta-Hydroxylase/antagonists & inhibitors
EDAT- 2005/12/31 09:00
MHDA- 2006/07/22 09:00
CRDT- 2005/12/31 09:00
PHST- 2005/09/16 00:00 [received]
PHST- 2005/10/17 00:00 [revised]
PHST- 2005/12/31 09:00 [pubmed]
PHST- 2006/07/22 09:00 [medline]
PHST- 2005/12/31 09:00 [entrez]
PST - ppublish
SO  - Pharmacol Rep. 2005 Nov-Dec;57(6):840-4.