Neuropsychopharmacology
March 9, 2005
Paul J Gresch, Randy L Smith, Robert J Barrett et al.
62 citations
Repeated administration of lysergic acid diethylamide (LSD) leads to tolerance, a decreased responsiveness to the drug. In rats trained to discriminate LSD from saline, five daily injections of a higher LSD dose caused a 44% reduction in their ability to recognize the drug. This behavioral tolerance was linked to reduced signaling through serotonin 5-HT2A receptors in the medial prefrontal cortex and anterior cingulate cortex, as shown by decreased G-protein coupling and lower receptor density. The findings suggest that adaptive changes in serotonin receptor signaling underlie tolerance to LSD's subjective effects.
Psychopharmacology
January 11, 2005
Michael A. Benneyworth, Randy L. Smith, Robert J. Barrett et al.
38 citations
The drug discrimination procedure, a common method for studying hallucinogens, was extended to mice. Mice required a nearly five-fold higher dose of LSD than rats to learn the discrimination. The LSD stimulus effects were dose-dependent and short-lived. A 5-HT(2A/2C) receptor agonist fully substituted for LSD, while a 5-HT(1A) agonist partially substituted. Antagonists selective for 5-HT(2A) or 5-HT(1A) receptors each only partially blocked LSD discrimination, indicating that both receptor types contribute to LSD's effects in mice.
Molecular Brain Research
March 1, 2003
Charles D. Nichols, Efrain E. Garcia, Elaine Sanders-Bush
1 citation
Lysergic acid diethylamide (LSD) transiently alters perception, behavior, and mood at very low doses, and its acute effects resemble symptoms of schizophrenia. Analyzing gene expression after LSD exposure is key to understanding how it changes behavior and to gaining insights into disorders like schizophrenia. Previous work identified a set of genes in the rat prefrontal cortex involved in synaptic plasticity that respond to LSD. This report details their expression using RNase protection analysis, showing a dynamic response: some genes increase and decrease rapidly, others change more gradually. Dose-response studies reveal two expression classes—maximally stimulated at lower doses or continuing to rise at higher doses. Most increases depend on the 5-HT(2A) receptor, but two genes involve neither 5-HT(1A) nor 5-HT(2A) receptors.