Expression of neurotrophins BDNF and NT-3, and their receptors in rat brain after administration of antipsychotic and psychotrophic agents

We have investigated the potential role of neurotrophic factors in antipsyc hotic drug action by examining the effects of antipsychotic and psychotropi c treatments on the mRNA expression of brain-derived neurotrophic factor (B DNF), neurotrophin-3 (NT-3), and their receptors, trkB and trkC, respective ly, in rat brain. Neither acute nor chronic clozapine treatment significant ly affected the expression of these mRNAs in any brain area investigated, e xcept for a decrease in trkB expression in the granule cells of the olfacto ry 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 cort ex, 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 att enuated by pre-treatment (1 h prior to MK-801 administration) with the anti psychotics, clozapine (25 mg/kg) and haloperidol (2 mg/kg), but not with th e antidepressant desipramine (15 mg/kg). Finally, we confirmed that the eff ects of MK-801 on BDNF mRNA were reflected in the respective changes in BDN F protein levels: MK-801 significantly increased anti-BDNF reactivity in th e entorhinal cortex (126 +/- 7% of control) while concomitantly decreasing in the hippocampus (71 +/- 2% of control). These data do not support the hy pothesis that neurotrophins play an important role in antipsychotic drug ac tion, but rather suggest that induction of BDNF in the entorhinal cortex ma y play a significant role in the psychotropic action of MK-801.