Behavioral characterization of dopamine D-5 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 abil ities, and neurological reflexes. Under basal conditions, D-5(-/-) mice wer e generally nor-mat on locomotor activity, the rotarod test, acoustic start le response, prepulse inhibition, elevated plus-maze, light <----> dark exp loration, Morris water maze, and cued and contextual fear conditioning. In the Porsolt forced swim test for antidepressant activity, male D-5(-/-) mic e 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 rece ptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic startl e 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-m ediated behaviors but may contribute to the pharmacological activation of d opaminergic pathways relevant to exploratory locomotion, startle, and prepu lse inhibition.