Background
There has been increasing evidence that atypical antipsychotics are effective in the
treatment of mood disorders or for augmenting 5-hydroxytryptamine selective reuptake
inhibitors for treatment-resistant depression.
Methods
Upregulation of neurogenesis in the adult hippocampus is a marker of antidepressant
activity, and the present study investigated the influence of the atypical antipsychotic
drug olanzapine on cell proliferation in the hippocampus of adult rat. The regulation
of cell proliferation in the prelimbic cortex of adult rat was also examined.
Results
Chronic (21 days) olanzapine administration increased the number of newborn cells
in the dentate gyrus of the hippocampus to the same extent as fluoxetine. Olanzapine
or fluoxetine treatment also increased the number of proliferating cells in the prelimbic
cortex. In contrast, there was no effect of either drug in the subventricular zone
or primary motor cortex, and there was a trend for an increase in the striatum. Subchronic
(7 days) administration of olanzapine had no effect on cell proliferation in hippocampus
or prelimbic cortex, consistent with the time course for the effect of fluoxetine
and the therapeutic actions of antidepressant treatment. The combination of olanzapine
plus fluoxetine did not result in a greater induction of cell proliferation in either
brain region. Analysis of the cell phenotype demonstrated that approximately 20% of
the newborn cells in the prelimbic cortex differentiated into endothelial cells but
not neurons, in contrast to the dentate gyrus, where most newborn cells differentiated
into neurons.
Conclusions
The results demonstrate that antidepressant or atypical antipsychotic medications
can increase the proliferation of glia in limbic brain structures, an effect that
could reverse the loss of glia that has been observed in depressed patients.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Autoradiographic investigation of cell proliferation in the brains of rats and cats. Postnatal growth and differentiation of the mammalian brain, with implications for a morphological theory of memory.Anat Rec. 1963; 145: 573-591
- Neuronal replacement form endogenous precursors in the adult brain after stroke.Nat Med. 2002; 8: 963-970
- Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone.Neuropsychopharmacology. 2004; 29: 450-460
- Newly generated neurons in the amygdala and adjoining cortex of adult primates.Proc Natl Acad Sci U S A. 2002; 99: 11464-11469
- Mood Disorders.Lippincott, Williams and Wilkins, New York2000
- MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.Am J Psychiatry. 1995; 152: 973-981
- Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus.J Comp Neurol. 2001; 435: 406-417
- Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder.Cereb Cortex. 2002; 12: 386-394
- Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.Arch Gen Psychiatry. 2001; 58: 545-553
- Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine.Proc Natl Acad Sci U S A. 2001; 98: 12796-12801
- Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus.J Neural Trans. 1998; 105: 317-327
- Subgenual prefrontal cortex abnormalities in mood disorders.Nature. 1997; 386: 824-827
- Depression.Biol Psychiatry. 2004; 56: 140-145
- Hippocampal changes in patients with a first episode of major depression.Am J Psychiatry. 2002; 159: 1112-1118
- Use of atypical antipsychotic agents in bipolar and schizoaffective disorders.J Clin Psychopharmacol. 1999; 19: 354-361
- Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation.J Neurosci. 1997; 17: 2492-2498
- Neurogenesis in the neocortex of adult primates.Science. 1999; 286: 548-552
- Adult-generated hippocampal and neocortical neurons in macaques have a transient existence.Proc Natl Acad Sci U S A. 2001; 98: 10910-10917
- Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus.Neuropsychopharmacology. 2004; 29: 1063-1069
- Changes in cognitive functioning with risperidone and olanzapine treatment.Psychopharmacology. 2003; 169: 404-411
- Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment.J Neurosci. 2002; 16: 283-290
- An open pilot study combining risperidone and a selective serotonin reuptake inhibitor as initial antidepressant therapy.J Clin Psychiatry. 2002; 63: 733-736
- Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo.Proc Natl Acad Sci U S A. 2002; 99: 11946-11950
- Neurogenesis in the 3-month-old rat visual cortex.J Comp Neurol. 1981; 195: 323-338
- Cognitive effects and antipsychotic treatment.Psychoneuroendocrinology. 2003; 28: 27-38
- Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys.J Neurosci. 2003; 23: 937-942
- Cell proliferation without neurogenesis in adult primate neocortex.Science. 2001; 294: 2127-2129
- Autoradiographic investigations of glial proliferation in the brain of adult mice. I. The DNA synthesis phase of neuroglia and endothelial cells.J Comp Neurol. 1973; 150: 169-175
- Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.Arch Gen Psychiatry. 1992; 49: 553-557
- Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens.J Pharmacol Exp Ther. 1999; 288: 774-781
- Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor.J Neurosci Res. 1999; 56: 72-75
- Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.Psychopharmacology. 1998; 136: 153-161
- Proliferation of mature oligodendrocytes after trauma to the central nervous system.Nature. 1984; 308: 274-275
- Course of illness, hippocampal function, and hippocampal volume in major depression.Proc Natl Acad Sci U S A. 2003; 100: 1387-1392
- Increased neurogenesis in a model of electroconvulsive therapy.Biol Psychiatry. 2000; 47: 1043-1049
Madsen TM, Yeh DD, Valentine GW, Duman RS (in press): Electroconvulsive seizure treatment increases cell proliferation in rat frontal cortex. Neuropsychopharmacology.
- Induction of neurogenesis in the neocortex of adult mice.Nature. 2000; 405: 951-955
- Cell proliferation in adult hippocampus is decreased by inescapable stress.Neuropsychopharmacology. 2003; 28: 1562-1571
- Chronic antidepressant treatment increases neurogenesis in adult hippocampus.J Neurosci. 2000; 20: 9104-9110
- Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro.Eur J Pharmacol. 2001; 411: 67-70
- The cellular neurobiology of depression.Nat Med. 2001; 7: 541-547
- Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders.Neuropsychopharmacology. 2003; 28: 402-412
- Postnatal formation of non-neuronal cells in the rat occipital cerebrum.J Comp Neurol. 1978; 177: 519-528
- Stress and hippocampal plasticity.Curr Opin Neurobiol. 1999; 5: 205-216
- Serotonin receptors.Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27: 1159-1172
- Quantitative MRI of the hippocampus and amygdala in severe depression.Psychol Med. 2000; 30: 117-125
- Regulation of neurogenesis in adult mouse hippocampus by cAMP and cAMP response element-binding protein.J Neurosci. 2002; 22: 3673-3682
- Neurobiology of depression.Neuron. 2002; 34: 13-25
- Gene profile of electroconvulsive seizures.J Neurosci. 2003; 23: 10841-10851
- Glial reduction in the subgenual prefrontal cortex in mood disorders.Proc Natl Acad Sci U S A. 1998; 95: 13290-13295
- Risperidone augmentation of SSRIs in major depression.J Clin Psychiatry. 1999; 60: 256-259
- Vascular niche for adult hippocampal neurogenesis.J Comp Neurol. 2000; 425: 479-494
- Magnetic-resonance morphometry in patients with major depression.Psychiatry Res. 1998; 84: 7-15
- The Rat Brain.3rd ed. Academic Press, San Diego1997
- Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol.Arch Gen Psychiatry. 2000; 57: 249-258
- Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex.J Neurosci. 2000; 20: 5012-5023
- Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.Biol Psychiatry. 1999; 45: 1085-1098
- Selective modulation of fibroblast growth factor-2 expression in the rat brain by the atypical antipsychotic clozapine.Neuropharmacology. 1999; 38: 1075-1082
- Challenges in the treatment of depression with psychotic features.Biol Psychiatry. 2003; 53: 680-690
- Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis.J Clin Psychiatry. 2002; 63: 1156-1163
- Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants.Science. 2003; 301: 805-809
- Cortical grey matter reduction associated with treatment-resistant chronic unipolar depression.Br J Psychiatry. 1998; 172: 527-532
- Antidepressant effect of the calcium-activated tyrosine kinase Pyk2 in the lateral septum.Biol Psychiatry. 2003; 54: 540-551
- Untreated depression and hippocampal volume loss.Am J Psychiatry. 2003; 160: 1-3
- Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression.J Neurosci. 1999; 19: 5034-5043
- Hippocampal atrophy in recurrent major depression.Proc Natl Acad Sci U S A. 1996; 93: 3908-3913
- The use of antidepressants in novel combination therapies.J Clin Psychiatry. 2003; 64: 14-18
- A novel augmentation strategy for treating resistant major depression.Am J Psychiatry. 2001; 158: 131-134
- Hippocampal volume in geriatric depression.Biol Psychiatry. 2000; 48: 301-309
- 5-HT2A receptor-mediated regulation of BDNF mRNA in the hippocampus and the neocortex.J Neurosci. 1997; 17: 2785-2795
- Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume.Mol Psychiatry. 2002; 7: 933-941
- Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder.Biol Psychiatry. 2003; 54: 693-702
- Atypical neuroleptics stimulate neurogenesis in adult rat brain.J Neurosci Res. 2002; 69: 72-79
- Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat.Neuropsychopharmacology. 2004; 29: 1230-1238
- A comparison of drug effects in latent inhibition and the forced swim test differentiates between the typical antipsychotic haloperidol, the atypical antipsychotics clozapine and olanzapine, and the antidepressants imipramine and paroxetine.Behav Pharmacol. 2003; 14: 215-222
- Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex.Neuropsychopharmacology. 2000; 23: 250-262
Article info
Publication history
Published online: September 06, 2004
Accepted:
July 14,
2004
Received in revised form:
June 25,
2004
Received:
March 8,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- ErratumBiological PsychiatryVol. 57Issue 2
- PreviewThere is an error in Table 2 within Kodama et al “Chronic Olanzapine or Fluoxetine Administration Increases Cell Proliferation in Hippocampus and Prefrontal Cortex of Adult Rats” Biological Psychiatry 56:570–580. The incorrect footnote is listed under column headings “Atypical APD” and “Typical APD” across from the row “Subventricular Zone.” Footnote e should replace footnote b in both instances. The corrected table appears below.
- Full-Text
- Preview
