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Psychedelic Definition & Meaning Both serotonin and DOI induced ERK1/2 phosphorylation in KO cells, but the degree of stimulation was much lower than in WT cells. Inhibition of PLC by U73122 (1-[6-[[(17β)-3-methoxyestra-1,3,5-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) blocked approximately one-third of serotonin-mediated activation of ERK1/2 in WT cells in the canonical pathway but completely blocked DOI-induced activation. In β-arrestin KO MEFs, U73122 completely prevented ERK1/2 phosphorylation induced by either serotonin or DOI. Thus, when the 5-HT2A receptor is expressed in MEF cells, DOI stimulates ERK1/2 primarily through a PLC-dependent pathway, whereas serotonin activates ERK1/2 predominantly through a β-arrestin–dependent pathway. Similar results were obtained with mescaline and DOI, in which no dose tested engendered significantly higher mean rates than did contingent saline. Mescaline transiently maintained significant self-administration in three monkeys, but th