| First Author | Svenningsson P | Year | 2003 |
| Journal | Science | Volume | 302 |
| Issue | 5649 | Pages | 1412-5 |
| PubMed ID | 14631045 | Mgi Jnum | J:107305 |
| Mgi Id | MGI:3620594 | Doi | 10.1126/science.1089681 |
| Citation | Svenningsson P, et al. (2003) Diverse psychotomimetics act through a common signaling pathway. Science 302(5649):1412-5 |
| abstractText | Three distinct classes of drugs: dopaminergic agonists (such as D-amphetamine), serotonergic agonists (such as LSD), and glutamatergic antagonists (such as PCP) all induce psychotomimetic states in experimental animals that closely resemble schizophrenia symptoms in humans. Here we implicate a common signaling pathway in mediating these effects. In this pathway, dopamine- and an adenosine 3',5'-monophosphate (cAMP)-regulated phospho-protein of 32 kilodaltons (DARPP-32) is phosphorylated or dephosphorylated at three sites, in a pattern predicted to cause a synergistic inhibition of protein phosphatase-1 and concomitant regulation of its downstream effector proteins glycogen synthesis kinase-3 (GSK-3), cAMP response element-binding protein (CREB), and c-Fos. In mice with a genetic deletion of DARPP-32 or with point mutations in phosphorylation sites of DARPP-32, the effects of D-amphetamine, LSD, and PCP on two behavioral parameters-sensorimotor gating and repetitive movements-were strongly attenuated. |
