Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration.
Lysergic acid diethylamide (LSD) is a psychoactive drug that transiently alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia. Characterizing gene expression profiles after LSD will be important for understanding how it alters behavior, and will lead to novel insights into disorders, such as schizophrenia, whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs. We previously identified a small collection of genes within the rat prefrontal cortex that respond to LSD. Many of the products of these genes are involved in the process of synaptic plasticity. In the current report, we present a detailed analysis of the expression of these genes within the brain using RNase protection analysis. We find that the gene response to LSD is quite dynamic. The expression of some genes increases rapidly and decreases rapidly, while other genes change more gradually. Dose-response studies show two classes of expression; gene expression maximally stimulated at lower doses, versus gene expression that continues to rise at the higher doses. The role of the 5-HT(1A) and 5-HT(2A) receptor in mediating the increases in gene expression was examined in a series of experiments using receptor specific antagonists. Most expression increases were due to activation of the 5-HT(2A) receptor, however expression of two genes had neither a 5-HT(1A) nor a 5-HT(2A) receptor component.
Nichols
Charles D
CD
Department of Pharmacology, Vanderbilt University School of Medicine, 8148 Medical Research Building Three, Nashville, TN 37232-8548, USA. charles.nichols@vanderbilt.edu
Garcia
Efrain E
EE
Sanders-Bush
Elaine
E
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000235:genetics; D006213:Hallucinogens / Q000494:pharmacology*; D000072233:Homer Scaffolding Proteins; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D051996:Transcription Factor RelA; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D002352:Carrier Proteins; D006213:Hallucinogens; D000072233:Homer Scaffolding Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D051996:Transcription Factor RelA; D012701:Serotonin; D012313:RNA; D008238:Lysergic Acid Diethylamide