Behavioral characterization of dopamine D₅ receptor null mutant mice

To study behavioral functions of the D₅ subtype, mice were generated with null mutations in the D₅ gene. This 1st behavioral characterization of D₅ null mutant mice (D₅ ^-/-) indicated normal general health, sensory abilities, and neurological reflexes. Under basal conditions, D₅ ^-/- 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 D₅ ^-/- mice showed lower levels of immobility. D₅ ^-/- mice showed some evidence of reduced responses to the hyperactivity-inducing effects of the D₁/D₅ receptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic startle and prepulse inhibition appeared to be attenuated in D₅ ^-/- mice. These results suggest that the D₅ 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.