Phenotypic, ethologically based resolution of spontaneous and D 2 ‐like vs D 1 ‐like agonist‐induced behavioural topography in mice with congenic D 3 dopamine receptor “knockout”

Uncertainty as to the functional role of the D 3 dopamine receptor, due primarily to a paucity of selective agonists or antagonists, is being addressed in mice with targeted gene deletion (“knockout”) thereof. This study describes, for the first time, the phenotype of congenic D 3 ‐null mice. Initially, 129/Sv × C57BL/6 D 3 ‐null mice were backcrossed 14 times onto C57BL/6; they were then assessed using an ethologically based approach which resolves all topographies of behaviour within the mouse repertoire. The ethogram of D 3 ‐null mice, on comparison with wildtypes, was characterised by no alteration in any topography of behaviour over an initial period of exploration; subsequent assessment over several hours revealed only increased rearing among females due to delayed habituation. Low doses of the selective D 2 ‐like agonist RU 24213 (0.016–0.25 mg/kg) inhibited topographies of exploratory behaviour; this effect was diminished in D 3 ‐null mice only when investigated following prolonged habituation, and then only for certain topographies of behaviour, primarily sniffing and rearing. High doses of RU 24213 (0.1–12.5 mg/kg) induced stereotyped sniffing and “ponderous” locomotion, while the selective D 1 ‐like agonist SK&F 83959 (0.016–2.0 mg/kg) promoted characteristic grooming syntax; these effects did not differ materially between the genotypes. When examined topographically on an essentially congenic C57BL/6 background (<0.005% 129/Sv), the resultant phenotype indicated essential conservation of the mouse ethogram, high‐dose D 2 ‐like stimulatory effects, and D 1 ‐like stimulatory effects in the absence of D 3 receptors. A role for D 3 receptors in inhibitory processes appeared topographically circumscribed and only when baseline levels of behaviour were low. Synapse 46:19–31, 2002. © 2002 Wiley‐Liss, Inc.