risperidone and haloperidol promote survival of stem cells in the rat hippocampus altered neuroplasticity contributes to the pathophysiology of schizophrenia however the idea that antipsychotics may act at least in part by normalizing neurogenesis has not been consistently supported our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine a validated model of schizophrenia and whether chronic administration with neuroleptic drugs haloperidol and risperidone affect changes of cell genesissurvival ketamine per se has no effect on cell proliferation its withdrawal however significantly induced cell proliferationsurvival in the hippocampus risperidone and haloperidol supported cell genesissurvival as well during ketamine withdrawal however their application did not affect cell proliferationsurvival additionally tunel staining indicated a cellprotective potency of both neuroleptics with respect to a ketamineinduced cell death as rtpcr and western blot revealed that the treatment effects of risperidone and haloperidol seemed to be mediated through activation of vegf and mmp2 the mrna expression of ngf bdnf and nt3 was unaffected from the respective receptors only trka was enhanced when ketamine withdrawal was combined with risperidone or haloperidol risperidone also induced bcl2 ketamine withdrawal has no effect on the expression of vegf mmp2 or bcl2 it activated the expression of bdnf this effect was normalized by risperidone or haloperidol the findings indicate a promoting effect of risperidone and haloperidol on survival of young neurons in the hippocampus by enhancing the expression of the antiapoptotic protein bcl2 and by activation of vegfmmp2 whereby an interference with ketamine and thus a priority role of the nmda system was not evident