PMID- 16391422
OWN - NLM
STAT- MEDLINE
DCOM- 20061207
LR  - 20181203
IS  - 0867-5910 (Print)
IS  - 0867-5910 (Linking)
VI  - 56
IP  - 4
DP  - 2005 Dec
TI  - Repeated treatment with mirtazepine induces brain-derived neurotrophic factor 
      gene expression in rats.
PG  - 661-71
AB  - Recent studies indicate a role of the brain-derived neurotrophic factor (BDNF) in 
      the pathophysiology of depression, as well as in the mechanism of action of 
      antidepressant drugs (ADs). It has been shown that serum BDNF levels are 
      decreased in depressed patients. Moreover, antidepressant treatment increases 
      serum BDNF levels and it is positively correlated with medication response. In 
      addition, repeated administration of ADs induces an increase in rat hippocampal 
      or cortical BDNF gene expression. Since the most potent effect of ADs on BDNF 
      gene expression was found after prolonged treatment, in the present study we 
      investigated the influence of repeated treatment (twice daily for 14 days) of the 
      new AD mirtazapine (5 or 10 mg/kg) on BDNF mRNA level (the Northern blot) in rat 
      hippocampus and cerebral cortex. Imipramine was used as a reference compound. The 
      experiment was carried out on male Wistar rats. The tissue for biochemical assays 
      was collected 24 h after the last doses of mirtazapine and imipramine. We also 
      studied the effect of repeated mirtazapine on the action of the 5-HT2A receptor 
      agonist (+/-)DOI in the behavioral test (head twitches induced by (+/-)DOI) in 
      rats. The obtained results showed that, like imipramine (10 mg/kg), mirtazapine 
      (10 mg/kg) increased BDNF gene expression in both the examined brain regions: in 
      the hippocampus by 24.0 and 26.5%, in the cerebral cortex by 29.9 and 41.5%, 
      respectively, compared with the vehicle-treated control. Neither mirtazapine nor 
      imipramine administered repeatedly at a lower dose (5 mg/kg) significantly 
      changed BDNF mRNA levels in the hippocampus and cerebral cortex. Repeated 
      treatment with mirtazapine (10, but not 5 mg/kg) inhibited the behavioral 
      syndrome induced by (+/-)DOI. This study provides first conclusive evidence that 
      repeated mirtazapine administration increases BDNF mRNA levels; moreover, it 
      indicates that the enhancement of BDNF gene expression may be essential for the 
      clinical effect of mirtazapine.
FAU - Rogoz, Z
AU  - Rogoz Z
AD  - Department of Pharmacology, Institute of Pharmacology, Polish Academy of 
      Sciences, Krakow, Poland. rogoz@if-pan.krakow.pl
FAU - Skuza, G
AU  - Skuza G
FAU - Legutko, B
AU  - Legutko B
LA  - eng
PT  - Journal Article
PL  - Poland
TA  - J Physiol Pharmacol
JT  - Journal of physiology and pharmacology : an official journal of the Polish 
      Physiological Society
JID - 9114501
RN  - 0 (Amphetamines)
RN  - 0 (Antidepressive Agents, Tricyclic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 250PJI13LM (Mianserin)
RN  - A051Q2099Q (Mirtazapine)
RN  - OGG85SX4E4 (Imipramine)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
SB  - IM
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Antidepressive Agents, Tricyclic/administration & dosage/*pharmacology
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/*metabolism
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Hippocampus/*drug effects/metabolism
MH  - Imipramine/administration & dosage/pharmacology
MH  - Male
MH  - Mianserin/administration & dosage/*analogs & derivatives/pharmacology
MH  - Mirtazapine
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Time Factors
EDAT- 2006/01/05 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/01/05 09:00
PHST- 2005/08/08 00:00 [received]
PHST- 2005/11/04 00:00 [accepted]
PHST- 2006/01/05 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/01/05 09:00 [entrez]
PST - ppublish
SO  - J Physiol Pharmacol. 2005 Dec;56(4):661-71.