Behavioral characterization of dopamine D5 receptor null mutant mice

To study behavioral functions of the D-5 subtype, mice were generated with null mutations in the D-5 gene. This I st behavioral characterization of D-5 null mutant mice (D-5(-/-)) indicated normal general health, sensory abilities, and neurological reflexes. Under basal conditions, D-5(-/-) mice were generally nor-mat on locomotor activity, the rotarod test, acoustic startle response, prepulse inhibition, elevated plus-maze, light <----> dark exploration, Morris water maze, and cued and contextual fear conditioning. In the Porsolt forced swim test for antidepressant activity, male D-5(-/-) mice showed lower levels of immobility. D-5(-/-) mice showed some evidence of reduced responses to the hyperactivity-inducing effects of the D-1/D-5 receptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic startle and prepulse inhibition appeared to be attenuated in D-5(-/-) mice, These results suggest that the D-5 receptor is not essential for many dopamine-mediated behaviors but may contribute to the pharmacological activation of dopaminergic pathways relevant to exploratory locomotion, startle, and prepulse inhibition.