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

Lysergic acid diethylamide (LSD) increases the expression of three specific genes in the mammalian prefrontal cortex: C/EBP-beta, a transcription factor; MKP-1, indicating activation of the MAP kinase pathway; and ILAD-1, which shows sequence similarity to arrestins. These expression changes are partially mediated through LSD interactions at 5-HT2A serotonin receptors. Evidence suggests alternative splicing at the ILAD-1 locus, with different splice isoforms responding differently at the transcriptional level to LSD. These findings help build a more complete picture of the complex intracellular events initiated by hallucinogens.

Study at a glance

Abstract

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-beta, 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-HT2A (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.