Hyperactivity and impaired response habituation in hyperdopaminergic mice.

Published

Journal Article

Abnormal dopaminergic transmission is implicated in schizophrenia, attention deficit hyperactivity disorder, and drug addiction. In an attempt to model aspects of these disorders, we have generated hyperdopaminergic mutant mice by reducing expression of the dopamine transporter (DAT) to 10% of wild-type levels (DAT knockdown). Fast-scan cyclic voltammetry and in vivo microdialysis revealed that released dopamine was cleared at a slow rate in knockdown mice, which resulted in a higher extracellular dopamine concentration. Unlike the DAT knockout mice, the DAT knockdown mice do not display a growth retardation phenotype. They have normal home cage activity but display hyperactivity and impaired response habituation in novel environments. In addition, we show that both the indirect dopamine receptor agonist amphetamine and the direct agonists apomorphine and quinpirole inhibit locomotor activity in the DAT knockdown mice, leading to the hypothesis that a shift in the balance between dopamine auto and heteroreceptor function may contribute to the therapeutic effect of psychostimulants in attention deficit hyperactivity disorder.

Full Text

Duke Authors

Cited Authors

  • Zhuang, X; Oosting, RS; Jones, SR; Gainetdinov, RR; Miller, GW; Caron, MG; Hen, R

Published Date

  • February 13, 2001

Published In

Volume / Issue

  • 98 / 4

Start / End Page

  • 1982 - 1987

PubMed ID

  • 11172062

Pubmed Central ID

  • 11172062

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.98.4.1982

Language

  • eng

Conference Location

  • United States