Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase‐1, C/EBP‐β and ILAD‐1 , a novel gene with homology to arrestins

We recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression patterns of a new collection of three genes increased in expression by acute LSD administration. These genes were identified through additional screens of Affymetrix DNA microarrays and examined in experiments to assess dose–response, time course and the receptor mediating the expression changes. The first induced gene, C/EBP‐β, is a transcription factor. The second gene, MKP‐1, suggests that LSD activates the MAP (mitogen activated protein) kinase pathway. The third gene, ILAD‐1 , demonstrates sequence similarity to the arrestins. The increase in expression of each gene was partially mediated through LSD interactions at 5‐HT 2A (serotonin) receptors. There is evidence of alternative splicing at the ILAD‐1 locus. Furthermore, data suggests that various splice isoforms of ILAD‐1 respond differently at the transcriptional level to LSD. The genes thus far found to be responsive to LSD are beginning to give a more complete picture of the complex intracellular events initiated by hallucinogens.