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DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.

Science (New York, N.Y.) (1998-08-07)
A A Fienberg, N Hiroi, P G Mermelstein, W Song, G L Snyder, A Nishi, A Cheramy, J P O'Callaghan, D B Miller, D G Cole, R Corbett, C N Haile, D C Cooper, S P Onn, A A Grace, C C Ouimet, F J White, S E Hyman, D J Surmeier, J Girault, E J Nestler, P Greengard
ABSTRACT

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.