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.
Holmes
A
A
Section on Behavioral Genomics, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1375, USA. aholmes@codon.nih.gov
Hollon
T R
TR
Gleason
T C
TC
Liu
Z
Z
Dreiling
J
J
Sibley
D R
DR
Crawley
J N
JN
D000818:Animals; D001143:Arousal / Q000235:genetics / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009042:Motivation; D009433:Neural Inhibition / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000502:physiology; D050641:Receptors, Dopamine D5; D013216:Reflex, Startle / Q000502:physiology
C493606:Drd5 protein, mouse; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5