title: Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents.
abstract: We have investigated the potential role of neurotrophic factors in antipsychotic drug action by examining the effects of antipsychotic and psychotropic treatments on the mRNA expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and their receptors, trkB and trkC, respectively, in rat brain. Neither acute nor chronic clozapine treatment significantly affected the expression of these mRNAs in any brain area investigated, except for a decrease in trkB expression in the granule cells of the olfactory bulb. We then examined the effects of the psychotropic agent MK-801. MK-801 (5 mg/kg; 4 h) significantly increased BDNF mRNA in the entorhinal cortex, but did not influence NT-3, trkB, or trkC expression in any brain area except for the olfactory bulb. The induction of BDNF mRNA by MK-801 was attenuated by pre-treatment (1 h prior to MK-801 administration) with the antipsychotics, clozapine (25 mg/kg) and haloperidol (2 mg/kg), but not with the antidepressant desipramine (15 mg/kg). Finally, we confirmed that the effects of MK-801 on BDNF mRNA were reflected in the respective changes in BDNF protein levels: MK-801 significantly increased anti-BDNF reactivity in the entorhinal cortex (126 +/- 7% of control) while concomitantly decreasing in the hippocampus (71 +/- 2% of control). These data do not support the hypothesis that neurotrophins play an important role in antipsychotic drug action, but rather suggest that induction of BDNF in the entorhinal cortex may play a significant role in the psychotropic action of MK-801.
authors.affiliation: A. I. Virtanen Institute, University of Kuopio, Finland.
authors.forename: A M
authors.initials: AM
authors.lastname: Lindén
authors.forename: J
authors.initials: J
authors.lastname: Väisänen
authors.forename: M
authors.initials: M
authors.lastname: Lakso
authors.forename: H
authors.initials: H
authors.lastname: Nawa
authors.forename: G
authors.initials: G
authors.lastname: Wong
authors.forename: E
authors.initials: E
authors.lastname: Castrén
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003024:Clozapine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D020933:Neurotrophin 3 / Q000235:genetics*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000235:genetics*; D020812:Receptor, trkC / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D011619:Psychotropic Drugs; D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D020813:Receptor, trkB; D020812:Receptor, trkC; D003024:Clozapine