Abstract
Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including hallucinations and detachment from reality. These remarkable behavioral effects have many similarities to the debilitating symptoms of neuropsychiatric disorders such as schizophrenia. The effects of hallucinogens are thought to be mediated by serotonin receptor activation; however, how these drugs elicit the unusual behavioral effects remains largely a mystery, despite much research. We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain. These studies represent a novel approach to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / drug effects*
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Brain / metabolism
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Early Growth Response Protein 2
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Gene Expression / drug effects*
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Gene Expression / physiology
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Genes, Immediate-Early / drug effects
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Genes, fos / drug effects
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Hallucinogens / pharmacology*
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I-kappa B Proteins*
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Immediate-Early Proteins
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Lysergic Acid Diethylamide / pharmacology*
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Male
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NF-KappaB Inhibitor alpha
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Oligonucleotide Array Sequence Analysis
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / genetics
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Receptors, Serotonin / biosynthesis
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
Substances
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Early Growth Response Protein 2
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Egr2 protein, rat
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Hallucinogens
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I-kappa B Proteins
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Immediate-Early Proteins
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NFKBIA protein, human
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Nerve Tissue Proteins
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Nfkbia protein, rat
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Nr4a3 protein, rat
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Nuclear Proteins
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RNA, Messenger
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Receptors, Serotonin
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Transcription Factors
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activity regulated cytoskeletal-associated protein
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NF-KappaB Inhibitor alpha
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Lysergic Acid Diethylamide
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase