Topographical evaluation of behavioural phenotype in a line of mice with targeted gene deletion of the D-2 dopamine receptor

The phenotype of spontaneous and dopamine D-2-like agonist-induced behaviou r was assessed topographically in a line of mice with targeted gene deletio n of the D-2 receptor. An ethologically-based, rapid time-sampling behaviou ral check-list technique was used to resolve and quantify all behaviours in the natural repertoire of the mouse. Relative to wildtypes [D-2(+/+)], D-2 -null [D-2(-/-)] mice evidenced over a 1 h period of initial exploration mo dest but significant reductions in locomotion, grooming, rearing free and r earing to wall, rearing seated, sniffing, sifting and stillness were not al tered. Individual elements of behaviour habituated similarly over a 6 h per iod for both genotypes. The dose-dependent induction of stereotyped sniffin g and ponderous locomotion by the D-2-like agonist RU 24213 (0.1-12.5 mg/kg ) in wildtypes was essentially absent in D-2-null mice. The ethogram of spo ntaneous behaviour in D-2-null mice was characterised by only modest reduct ions in, and topographical shifts between, certain individual elements of b ehaviour. Essential abolition of D-2-like agonist responsivity in D-2-null mice vis-h vis considerable preservation of spontaneous behavioural topogra phy suggests compensatory processes subsequent to developmental absence of the D-2 receptor that are able to sustain function under naturalistic, toni c conditions but not during phasic challenge. (C) 2000 Elsevier Science Ltd . All rights reserved.