Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration.
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.
Angelucci
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F
Karolinska Institutet, Department of Clinical Neuroscience, St. Göran's Hospital, Stockholm, Sweden.
Mathé
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AA
Aloe
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L
D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D006220:Haloperidol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism*; D018967:Risperidone / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D006220:Haloperidol; D018967:Risperidone