Paradoxical locomotor behavior of dopamine D1 receptor transgenic mice.

Abstract:

:The behavioral effects of augmenting dopamine D1 receptor expression in the brain were investigated in mice incorporating additional copies of the mouse D1 receptor gene. Two transgenic lines showed increases in brain D1 receptor binding sites, which were greatest in extrastriatal regions. The full D1 agonist SKF 81297, when administered systemically to control animals, stimulated a dose-dependent increase in locomotor activity. In contrast, in D1 receptor overexpressing transgenic mice, this drug caused a marked suppression of locomotion due to a decrease in the frequency of movement initiation. Amphetamine and cocaine induced comparable locomotor activation in both transgenic animals and their control littermates. In the transgenic animals, D1 agonist-induced rearing and climbing behaviors were suppressed. However, on rotarod testing, the agonist-treated transgenic and control mice performed comparably, indicating that sensorimotor coordination was unaffected. These studies demonstrate that altering the levels of D1 receptor expression reverses the effects of D1 agonism on locomotor initiation and rearing.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Dracheva S,Xu M,Kelley KA,Haroutunian V,Holstein GR,Haun S,Silverstein JH,Sealfon SC

doi

10.1006/exnr.1999.7037

keywords:

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

169-79

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(99)97037-1

journal_volume

157

pub_type

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