PMID- 10861791
OWN - NLM
STAT- MEDLINE
DCOM- 20000906
LR  - 20220310
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 60
IP  - 6
DP  - 2000 Jun 15
TI  - Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain 
      are significantly altered after haloperidol and risperidone administration.
PG  - 783-94
AB  - The antipsychotics haloperidol and risperidone are widely used in the therapy of 
      schizophrenia. The former drug mainly acts on the dopamine (DA) D(2) receptor 
      whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly 
      in the neurons of striatal and limbic structures. Recent evidence suggests that 
      neurotrophins might also be involved in antipsychotic action in the central 
      nervous system (CNS). We have previously reported that haloperidol and 
      risperidone significantly affect brain nerve growth factor (NGF) level suggesting 
      that these drugs influence the turnover of endogenous growth factors. 
      Brain-derived neurotrophic factor (BDNF) supports survival and differentiation of 
      developing and mature brain DA neurons. We hypothesized that treatments with 
      haloperidol or risperidone will affect synthesis/release of brain BDNF and tested 
      this hypothesis by measuring BDNF and TrkB in rat brain regions after a 
      29-day-treatment with haloperidol or risperidone added to chow. Drug treatments 
      had no effects on weight of brain regions. Chronic administration of these drugs, 
      however, altered BDNF synthesis or release and expression of 
      TrkB-immunoreactivity within the brain. Both haloperidol and risperidone 
      significantly decreased BDNF concentrations in frontal cortex, occipital cortex 
      and hippocampus and decreased or increased TrkB receptors in selected brain 
      structures. Because BDNF can act on a variety of CNS neurons, it is reasonable to 
      hypothesize that alteration of brain level of this neurotrophin could constitute 
      one of the mechanisms of action of antipsychotic drugs. These observations also 
      support the possibility that neurotrophic factors play a role in altered brain 
      function in schizophrenic disorders.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Angelucci, F
AU  - Angelucci F
AD  - Karolinska Institutet, Department of Clinical Neuroscience, St. Goran's Hospital, 
      Stockholm, Sweden.
FAU - Mathe, A A
AU  - Mathe AA
FAU - Aloe, L
AU  - Aloe L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - J6292F8L3D (Haloperidol)
RN  - L6UH7ZF8HC (Risperidone)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/blood/metabolism/*pharmacology
MH  - Body Weight/drug effects
MH  - Brain/anatomy & histology/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Feeding Behavior/drug effects
MH  - Haloperidol/blood/metabolism/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mesencephalon/drug effects/metabolism
MH  - Organ Size/drug effects
MH  - Osmolar Concentration
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, trkB/*metabolism
MH  - Risperidone/blood/metabolism/*pharmacology
MH  - Time Factors
EDAT- 2000/06/22 10:00
MHDA- 2000/09/09 11:01
CRDT- 2000/06/22 10:00
PHST- 2000/06/22 10:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/06/22 10:00 [entrez]
AID - 10.1002/1097-4547(20000615)60:6<783::AID-JNR11>3.0.CO;2-M [pii]
AID - 10.1002/1097-4547(20000615)60:6<783::AID-JNR11>3.0.CO;2-M [doi]
PST - ppublish
SO  - J Neurosci Res. 2000 Jun 15;60(6):783-94. doi: 
      10.1002/1097-4547(20000615)60:6<783::AID-JNR11>3.0.CO;2-M.