Serotonergic basis of antipsychotic drug effects in schizophrenia. 1998

J A Lieberman, and R B Mailman, and G Duncan, and L Sikich, and M Chakos, and D E Nichols, and J E Kraus
Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Recent attention has been focused on the involvement of serotonin (5-HT) in the pathophysiology of schizophrenia and its role in mediating antipsychotic drug effects. There are two reasons for the new emphasis: the tremendous success of the so-called "atypical" antipsychotic drugs (a common feature of which is their high affinity for specific 5-HT receptor subtypes); and the elucidation of a complex family of 5-HT receptors whose function and pharmacology is only beginning to be understood. This paper will review the evidence that pertains to the role of 5-HT in mediating antipsychotic drug effects. The interaction of dopamine and 5-HT systems will be reviewed, and the mechanisms of action of atypical antipsychotic drugs will be evaluated in this context. The impact of serotonin on neurodevelopment, and the involvement of serotonin in the psychotomimetic and psychotogenic properties of hallucinogens, will be discussed. Together, these facts will be placed into the context of changes in serotonergic function in schizophrenia.

UI MeSH Term Description Entries
D011903 Raphe Nuclei Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA. Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012559 Schizophrenia A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras
D014055 Tomography, Emission-Computed Tomography using radioactive emissions from injected RADIONUCLIDES and computer ALGORITHMS to reconstruct an image. CAT Scan, Radionuclide,CT Scan, Radionuclide,Computerized Emission Tomography,Radionuclide Tomography, Computed,Scintigraphy, Computed Tomographic,Tomography, Radionuclide-Computed,Computed Tomographic Scintigraphy,Emission-Computed Tomography,Radionuclide Computer-Assisted Tomography,Radionuclide Computerized Tomography,Radionuclide-Computed Tomography,Radionuclide-Emission Computed Tomography,Tomography, Computerized Emission,CAT Scans, Radionuclide,CT Scans, Radionuclide,Computed Radionuclide Tomography,Computed Tomography, Radionuclide-Emission,Computer-Assisted Tomographies, Radionuclide,Computer-Assisted Tomography, Radionuclide,Computerized Tomography, Radionuclide,Emission Computed Tomography,Emission Tomography, Computerized,Radionuclide CAT Scan,Radionuclide CAT Scans,Radionuclide CT Scan,Radionuclide CT Scans,Radionuclide Computed Tomography,Radionuclide Computer Assisted Tomography,Radionuclide Computer-Assisted Tomographies,Radionuclide Emission Computed Tomography,Scan, Radionuclide CAT,Scan, Radionuclide CT,Scans, Radionuclide CAT,Scans, Radionuclide CT,Tomographic Scintigraphy, Computed,Tomographies, Radionuclide Computer-Assisted,Tomography, Computed Radionuclide,Tomography, Emission Computed,Tomography, Radionuclide Computed,Tomography, Radionuclide Computer-Assisted,Tomography, Radionuclide Computerized,Tomography, Radionuclide-Emission Computed

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