A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.
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.
Nichols
Charles D
CD
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Sanders-Bush
Elaine
E
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051767:Early Growth Response Protein 2; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D017781:Genes, Immediate-Early / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D006213:Hallucinogens; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D008238:Lysergic Acid Diethylamide; D000072000:NF-KappaB Inhibitor alpha; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C497328:Egr2 protein, rat; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; C091333:Nr4a3 protein, rat; C092069:activity regulated cytoskeletal-associated protein