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Publication : Paradoxical locomotor behavior of dopamine D1 receptor transgenic mice.

First Author  Dracheva S Year  1999
Journal  Exp Neurol Volume  157
Issue  1 Pages  169-79
PubMed ID  10222120 Mgi Jnum  J:70445
Mgi Id  MGI:2137377 Doi  10.1006/exnr.1999.7037
Citation  Dracheva S, et al. (1999) Paradoxical locomotor behavior of dopamine D1 receptor transgenic mice. Exp Neurol 157(1):169-79
abstractText  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.
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