PMID- 12393228
OWN - NLM
STAT- MEDLINE
DCOM- 20030124
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 954
IP  - 1
DP  - 2002 Nov 1
TI  - Differential regulation of hippocampal BDNF mRNA by typical and atypical 
      antipsychotic administration.
PG  - 11-20
AB  - Apart from their differential propensities to block dopamine D2 and serotonin 
      5-HT2 receptors, the molecular mechanisms underlying the clinical efficacy of 
      typical and atypical antipsychotics in schizophrenia are largely unknown. Given 
      recent interest in the effects of antipsychotics on neurotrophic and other growth 
      related factors, the effects of antipsychotics on brain-derived neurotrophic 
      factor (BDNF), a neurotrophin crucial to the structural integrity of adult 
      neurons, were investigated in male Wistar rats. Chronic (19 day) but not acute 
      (45 min) antipsychotic administration significantly altered levels of hippocampal 
      BDNF mRNA. In addition, whereas chronic treatment with the strong D2 
      receptor-blocker haloperidol significantly downregulated hippocampal BDNF mRNA, 
      the selective 5-HT2 receptor-blocker ritanserin significantly upregulated CA1 
      hippocampal BDNF mRNA in comparison to controls. Since high doses of risperidone 
      and clozapine produce potent inhibition of both 5-HT2 and D2 receptors, while 
      lower doses produce significantly greater 5-HT2 vs. D2 receptor blockade, a 
      dose-response study was employed to determine whether low doses of these atypical 
      antipsychotics would also upregulate hippocampal BDNF mRNA in the absence of 
      significant D2 receptor blockade. Whereas chronic haloperidol and high-dose 
      risperidone significantly downregulated hippocampal BDNF mRNA, intermediate and 
      lower doses of risperidone and clozapine were, unlike ritanserin, without effect 
      when compared to controls. Thus, although the long-term downregulation of 
      hippocampal BDNF mRNA may underlie the different clinical profiles of certain 
      antipsychotics, this effect seems to be associated with antipsychotic doses that 
      not only cause significant D2 receptor inhibition, but are usually associated 
      with side effects rather than therapeutic efficacies.
FAU - Chlan-Fourney, Jennifer
AU  - Chlan-Fourney J
AD  - Neuropsychiatry Research Unit, Department of Psychiatry, University of 
      Saskatchewan, A114 Medical Research Building, 103 Wiggins Rd, Saskatoon, 
      Saskatchewan S7N 5E4, Canada. jennifer.chlan-fourney@uth.tmc.edu
FAU - Ashe, Paula
AU  - Ashe P
FAU - Nylen, Kirk
AU  - Nylen K
FAU - Juorio, Augusto V
AU  - Juorio AV
FAU - Li, Xin Min
AU  - Li XM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine D2 Receptor Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0223RD59PE (Remoxipride)
RN  - 145TFV465S (Ritanserin)
RN  - J60AR2IKIC (Clozapine)
RN  - J6292F8L3D (Haloperidol)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*pharmacology
MH  - Blotting, Northern
MH  - Brain-Derived Neurotrophic Factor/*drug effects/genetics/metabolism
MH  - Clozapine/administration & dosage/pharmacology
MH  - Dopamine D2 Receptor Antagonists
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Gene Expression Regulation/drug effects
MH  - Haloperidol/pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - In Situ Hybridization
MH  - Male
MH  - RNA, Messenger/*drug effects/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Remoxipride/pharmacology
MH  - Risperidone/administration & dosage/pharmacology
MH  - Ritanserin/pharmacology
MH  - Time Factors
EDAT- 2002/10/24 04:00
MHDA- 2003/01/25 04:00
CRDT- 2002/10/24 04:00
PHST- 2002/10/24 04:00 [pubmed]
PHST- 2003/01/25 04:00 [medline]
PHST- 2002/10/24 04:00 [entrez]
AID - S0006899302032158 [pii]
AID - 10.1016/s0006-8993(02)03215-8 [doi]
PST - ppublish
SO  - Brain Res. 2002 Nov 1;954(1):11-20. doi: 10.1016/s0006-8993(02)03215-8.