Abstract
There have been repeated reports of a decrease in serotonin2A receptors in the frontal cortex from subjects with schizophrenia. Similarly, in rats treated with antipsychotic drugs, it has been shown that many antipsychotic drugs decrease cortical serotonin2A receptors, an affect not seen with the antipsychotic drug haloperidol. We therefore compared the density of serotonin2A receptors in frontals cortex from schizophrenic subjects treated with haloperidol, schizophrenic subjects treated with other antipsychotic drugs, and nonschizophrenic subjects. Independent of antipsychotic drug treatment, serotonin2A receptors were decreased in the frontal cortex from schizophrenic subjects. Importantly, the density of serotonin2A receptors was not different in schizophrenic subjects whether or not they had been treated with haloperidol. This study suggests that data obtained from treating rats with antipsychotic drugs cannot be simplistically extrapolated to studies on tissue obtained postmortem from schizophrenic subjects treated with the same drugs.
Similar content being viewed by others
References
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., rev. American Psychiatric Association, Washington, DC.
Andree T. H., Mikuni M., Tong C. Y., Koenig J. I., and Meltzer H. Y. (1986) Differential effect of subchronic treatment with various neuroleptic agents on serotonin 2 receptors in rat cerebral cortex.J. Neurochem. 46, 191–197.
Andrews G., Hall W., Goldstein G., Lapsley H., Bartels R., and Silove D. (1985) The economic costs of schizophrenia.Arch. Gen. Psychiatry 42, 537–543.
Arora R. C. and Meltzer H. Y. (1991) Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients.J. Neural. Transm. Gen. Sect. 85, 19–29.
Buckland P. R., D’Souza U., Maher N. A., and McGuffin P. (1997) The effects of antipsychotic drugs on the mRNA levels of serotonin 5HT2A and 5HT2C receptors.Mol. Brain. Res. 48, 45–52.
Burnet P. W., Chen C. P. L. H., McGowan S., Franklin M., and Harrison, P. J. (1996a) The effects of clozapine and haloperidol on serotonin-1A, −2A and −2C receptor gene expression and serotonin metabolism in the rat forebrain.Neuroscience 73, 531–540.
Burnet P. W., Eastwood S. L., and Harrison P. J. (1996b) 5-HT1A and 5-HT2A receptor mRNA and binding site densities are differentially altered in schizophrenia.Neuropsychopharmacology 15, 442–455.
Creese I., Burt D. R., and Snyder S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs.Science 192, 481–483.
Dean B. and Hayes W. (1996) Decreased frontal cortical serotonin2A receptors in subjects with schizophrenia.Schizophr. Res. 21, 133–139.
Eison A. S., Yocca F. D., and Gianutsos G. (1991) Effect of chronic administration of anti-depressant drugs on 5-HT2-mediated behaviour in rat following noradrenergic or serotonergic denervation.J. Neural. Trans. Gen. Sect. 84, 32.
Foster, P. (1989) Neuroleptic equivalence.Pharm. J. 243, 431–432.
Fuster J. M. (1989)The Prefrontal Cortex. Raven, New York.
Fuxe K., Ogren S.-O., Agnati L. F., Benfenati F., Fredholm B., Andersson K., et al. (1983) Chronic antidepressant treatment and central 5-HT synapses.Neuropharmacology 22, 389–400.
Gurevich E. V. and Joyce J. N. (1997) Alterations in the cortical serotonergic system in schizophrenia: A postmortem study.Biol. Psychiatry 42, 529–545.
Hashimoto T., Kitamura N., Kajimoto Y., Shirai Y., Shirakawa O., Mita T. et al. (1993) Differential changes in serotonin 5-HT1A and 5-HT2 receptor binding in patients with chronic schizophrenia.Psychopharmacology (Berl.) 112, S35-S39.
Hill C., Keks N. A., Roberts S., Opeskin K., Dean B., and Copolov D. L. (1996) Postmortem brain studies in schizophrenia: The problems of diagnosis.Am. J. Psychiatry 153, 533–537.
Hrdina P. D. and Vu T. B. (1993) Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: An autoradiographic study.Synapse 14, 324–331.
Huang N., Ase A. R., Herbert C., Van Gelder N. N., and Reader T. A. (1997) Effects of chronic neuroleptic treatments on dopamine D1 and D2 receptors: Homogenate binding and autoradiographic studies.Neurochem. Int. 30, 277–290.
Kerwin R. W. (1994) The new atypical antipsychotics: A lack of extrapyramidal sideeffects and new routes in schizophrenia.Br. J. Psychiatry 164, 141–148.
Laruelle M., Abi-Dargham A., Casanova M. F., Toti, R., Weinberger D. R., and Kleinman J. E. (1993) Selective abnormalities of prefrontal serotonergic receptors in schizophrenia: A postmortem study.Arch. Gen. Psychiatry 50, 810–818.
Lee T. and Tang S. W. (1984) Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain.Psychiatry Res. 12, 277–285.
Matsubara S. and Meltzer H. Y. (1989) Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex.Life Sci. 45, 1397–1406.
Mikuni M. and Meltzer H. Y. (1984) Reduction of serotonin2 receptors in rat cerebral cortex after subchronic administration of imipramine, chlorpromazine, and the combination thereof.Life Sci. 34, 87–92.
Mita T., Hanada S., Nishino N., Kuno T., Nakai H., Yamadori Y., et al. (1986) Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics.Biol. Psychiatry 21, 1407–1414.
Nowak G., Arnt J., Hyttel J., and Svendsen O. (1985) Down-regulation of dopamine D-2, 5-HT2 receptors and beta-adrenoceptors in rat brains after prolonged treatments with a new potential antidepressant, Lu 19-005.J. Neural Transm. 64, 227–238.
O’Dell S. J., La Hoste G. J., Widmark C. B., Shapiro R. M., Potkin S. G., and Marshall J. F. (1990) Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in the rat brain.Synapse 6, 146–153.
Peroutka S. J. and Snyder S. H. (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding.Science 210, 88–90.
Schoups A. A. and De Potter, W. P. (1988) Species dependence of adaptations at the pre- and postsynaptic serotonergic receptors following long-term antidepressant drug treatment.Biochem. Pharmacol. 37, 4451–4460.
Seeman P. and Lee T. (1975) Antipsychotic drugs: Direct correlation between clinical potency and presynaptic action on dopamine neurons.Science 188, 1217–1219.
Stolz J. F., Marsden C. A., and Middlemiss D. N. (1983) Effect of chronic antidepressant treatment and subsequent withdrawal on [3H]-5-hydroxytryptamine and [3H]spiperone binding in rat frontal cortex and serotonin receptor mediated behaviour.Psychopharmacology 80, 155.
Wamsley J. K., Byerley W. F., McCabe R. T., McConnell E. J., Dawson T. M., and Grosser B. I. (1987) Receptor alterations associated with serotonergic agents: An autoradiographic analysis.J. Clin. Psychiatr. 48 (Suppl) 19–25.
Wilmot C. A. and Szczepanik A. M. (1989) Effect of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT2) and dopamine (D2) receptors in rat brain.Brain Res. 487, 288–298.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dean, B., Hayes, W., Hill, C. et al. Decreased serotonin2A receptors in Brodmann’s area 9 from schizophrenic subjects. Molecular and Chemical Neuropathology 34, 133–145 (1998). https://doi.org/10.1007/BF02815075
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02815075