Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration
Charles D. Nichols, Efrain E. Garcia, Elaine Sanders‐bush
Brain research. Molecular brain research March 1, 2003 DOI: 10.1016/s0169-328x(03)00029-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rat prefrontal cortex |
| Intervention | LSD |
| Topics | LSD Serotonin |
| Keywords | Prefrontal cortex Gene expression Genetics Cognition Receptor |
| Citations | 1 |
| Key findings | Gene expression in the rat prefrontal cortex after LSD is dynamic and mostly mediated by the 5-HT(2A) receptor, with two genes showing no dependence on 5-HT(1A) or 5-HT(2A) receptors. |
Abstract
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.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 46
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics Frontiers in Psychiatry September 10, 2021
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Psychedelic Drugs in Biomedicine TIPS - Trends in Pharmacological Sciences September 22, 2017
and 41 more in the library
Cites 13
- Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release Brain Research April 1, 1999
- Visual Phenomenology of the LSD Flashback Archives of General Psychiatry August 1, 1983
- A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain Neuropsychopharmacology May 1, 2002
- Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD) Journal of Medicinal Chemistry September 1, 2002
- The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacology, Biochemistry, and Behavior 2000
and 8 more in the library