Robert J. Barrett

2 papers in the library · 100 citations · publishing 2005

Papers

Behavioral Tolerance to Lysergic Acid Diethylamide is Associated with Reduced Serotonin-2A Receptor Signaling in Rat Cortex

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.

DOI: 10.1038/sj.npp.1300711 Full text Lysergic acid diethylamide Serotonin Prefrontal cortex Psychology +8

Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice

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.

DOI: 10.1007/s00213-004-2108-z Lysergic acid diethylamide Pharmacology Hallucinogen Antagonist +6