Paradoxical locomotor behavior of dopamine D1 receptor transgenic mice

The behavioral effects of augmenting dopamine D1 receptor expression in the brain were investigated in mice incorporating additional copies of the mou se D1 receptor gene. Two transgenic lines showed increases in brain D1 rece ptor binding sites, which were greatest in extrastriatal regions. The full D1 agonist SKF 81297, when administered systemically to control animals, st imulated a dose-dependent increase in locomotor activity. In contrast, in D 1 receptor overexpressing transgenic mice, this drug caused a marked suppre ssion of locomotion due to a decrease in the frequency of movement initiati on 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. Howeve r, on rotarod testing, the agonist-treated transgenic and control mice perf ormed comparably, indicating that sensorimotor coordination was unaffected. These studies demonstrate that altering the levels of D1 receptor expressi on reverses the effects of D1 agonism on locomotor initiation and rearing. (C) 1999 Academic Press.