Editors' ChoiceBRAIN DISEASE

Central Lynch Pin in Psychosis

Science's STKE  25 Nov 2003:
Vol. 2003, Issue 210, pp. tw459-TW459
DOI: 10.1126/stke.2102003TW459

The causes of some mental illnesses such as schizophrenia have been very difficult to pin down, probably because numerous neurotransmitter systems go awry in the brains of such patients. This apparent complexity may be because each of these transmitters activates a common downstream pathway that causes the negative symptoms of the disease. Mice injected with drugs that activate various transmitter pathways (amphetamines, LSD, and PCP) all exhibit psychosis-like symptoms. Svenningsson et al. show that phosphorylation of the protein DARPP-32 at specific sites is necessary for each of the drugs to have these effects. Mice that did not have the ability to phosphorylate DARPP-32 did not show psychosis-like behaviors in response to these three different drugs.

P. Svenningsson, E. T. Tzavara, R. Carruthers, I. Rachleff, S. Wattler, M. Nehls, D. L. McKinzie, A. A. Fienberg, G. G. Nomikos, P. Greengard, Diverse psychotomimetics act through a common signaling pathway. Science 302, 1412-1415 (2003). [Abstract] [Full Text]