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 1st 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 normal 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.