Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in ratbrain are significantly altered after haloperidol and risperidone administration

The antipsychotics haloperidol and risperidone are widely used in the thera py of schizophrenia. The former drug mainly acts on the dopamine (DA) D-2 r eceptor whereas risperidone binds to both DA and serotonin (5HT) receptors, particularly in the neurons of striatal and limbic structures. Recent evid ence suggests that neurotrophins might also be involved in antipsychotic ac tion 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 endogenou s growth factors. Brain-derived neurotrophic factor (BDNF) supports surviva l and differentiation of developing and mature brain DA neurons. We hypothe sized that treatments with haloperidol or risperidone will affect synthesis /release of brain BDNF and tested this hypothesis by measuring BDNF and Trk B in rat brain regions after a 29-day-treatment with haloperidol or risperi done added to chow. Drug treatments had no effects on weight of brain regio ns. Chronic administration of these drugs, however, altered BDNF synthesis or release and expression of TrkB-immunoreactivity within the brain. Both h aloperidol and risperidone significantly decreased BDNF concentrations in f rontal cortex, occipital cortex and hippocampus and decreased or increased TrkB receptors in selected brain structures. Because BDNF can act on a vari ety of CNS neurons, it is reasonable to hypothesize that alteration of brai n level of this neurotrophin could constitute one of the mechanisms of acti on of antipsychotic drugs. These observations also support the possibility that neurotrophic factors play a role in altered brain function in schizoph renic disorders. J. Neurosci. Res. 60:783-794, 2000. (C) 2000 Wiley-Liss, I nc.