PMID- 22575330
OWN - NLM
STAT- MEDLINE
DCOM- 20121204
LR  - 20221207
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Linking)
VI  - 46
IP  - 8
DP  - 2012 Aug
TI  - The administration of olanzapine and fluoxetine has synergistic effects on 
      intracellular survival pathways in the rat brain.
PG  - 1029-35
LID - 10.1016/j.jpsychires.2012.04.016 [doi]
AB  - Recently, several studies have emerged suggesting a role of the intracellular 
      survival pathways in the treatment of mood disorders. In addition, the beneficial 
      effects of using a combination of antipsychotics and antidepressants have been 
      shown. With this in mind, we evaluated the effects of the acute administration of 
      fluoxetine (FLX), olanzapine (OLZ) and the combination of fluoxetine/olanzapine 
      on the brain-derived-neurotrophic factor (BDNF), cAMP response element-binding 
      (CREB), Protein Kinase B (PKB, Akt), B-cell lymphoma 2 (Bcl-2) and 
      Bcl-2-associated death promoter (BAD) in the rat brain. Adult Wistar rats 
      received an acute injection of OLZ (3 or 6 mg/kg) and/or FLX (12.5 or 25 mg/kg), 
      and were evaluated for Akt, BDNF, CREB, Bcl-2 and BAD protein levels in the 
      prefrontal cortex, hippocampus and striatum. Our results showed that treatment 
      with FLX and OLZ alone or in combination increased the Akt, CREB, BDNF, Bcl-2 and 
      BAD levels in the prefrontal cortex, hippocampus and striatum. However, the 
      combination of FLX and OLZ at high doses was associated with a greater increase 
      in the levels of Akt in the prefrontal cortex, and did not have an effect on the 
      levels of BAD in any of the brain areas that we evaluated. Finally, these 
      findings further support the hypothesis that treatment with FLX and OLZ alone or 
      in combination exert neuroprotective effects, and that intracellular survival 
      pathways could be involved in the therapeutic effects of combining antipsychotic 
      and antidepressant drugs in mood disorders.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Reus, Gislaine Z
AU  - Reus GZ
AD  - Laboratorio de Neurociencias, Instituto Nacional de Ciencia e Tecnologia 
      Translacional em Medicina (INCT-TM), and Nucleo de Excelencia em Neurociencias 
      Aplicadas de Santa Catarina, Unidade Academica de Ciencias da Saude, Universidade 
      do Extremo Sul Catarinense, Criciuma, SC, Brazil. gislainezilli@hotmail.com
FAU - Abelaira, Helena M
AU  - Abelaira HM
FAU - Agostinho, Fabiano R
AU  - Agostinho FR
FAU - Ribeiro, Karine F
AU  - Ribeiro KF
FAU - Vitto, Marcelo F
AU  - Vitto MF
FAU - Luciano, Thais F
AU  - Luciano TF
FAU - Souza, Claudio T de
AU  - Souza CT
FAU - Quevedo, Joao
AU  - Quevedo J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120508
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Bad protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Drug Combinations)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (bcl-Associated Death Protein)
RN  - 0 (olanzapine-fluoxetine combination)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 12794-10-4 (Benzodiazepines)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Benzodiazepines/*administration & dosage
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Drug Synergism
MH  - Fluoxetine/*administration & dosage
MH  - Male
MH  - Neuroprotective Agents/*administration & dosage
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Selective Serotonin Reuptake Inhibitors/*administration & dosage
MH  - Signal Transduction/*drug effects
MH  - bcl-Associated Death Protein/metabolism
EDAT- 2012/05/12 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/05/12 06:00
PHST- 2012/03/07 00:00 [received]
PHST- 2012/04/12 00:00 [revised]
PHST- 2012/04/13 00:00 [accepted]
PHST- 2012/05/12 06:00 [entrez]
PHST- 2012/05/12 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S0022-3956(12)00130-6 [pii]
AID - 10.1016/j.jpsychires.2012.04.016 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2012 Aug;46(8):1029-35. doi: 10.1016/j.jpsychires.2012.04.016. 
      Epub 2012 May 8.