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.