Topographical evaluation of behavioural phenotype in a line of mice with targeted gene deletion of the D2 dopamine receptor.
The phenotype of spontaneous and dopamine D2-like agonist-induced behaviour was assessed topographically in a line of mice with targeted gene deletion of the D1 receptor. An ethologically-based, rapid time-sampling behavioural check-list technique was used to resolve and quantify all behaviours in the natural repertoire of the mouse. Relative to wildtypes [D2+/+], D2-null [D2-/-] mice evidenced over a 1 h period of initial exploration modest but significant reductions in locomotion, grooming, rearing free and rearing to wall; rearing seated, sniffing, sifting and stillness were not altered. Individual elements of behaviour habituated similarly over a 6 h period for both genotypes. The dose-dependent induction of stereotyped sniffing and ponderous locomotion by the D2-like agonist RU 24213 (0.1-12.5 mg/kg) in wildtypes was essentially absent in D2-null mice. The ethogram of spontaneous behaviour in D2-null mice was characterised by only modest reductions in, and topographical shifts between, certain individual elements of behaviour. Essential abolition of D2-like agonist responsivity in D2-null mice vis-à-vis considerable preservation of spontaneous behavioural topography suggests compensatory processes subsequent to developmental absence of the D2 receptor that are able to sustain function under naturalistic, tonic conditions but not during phasic challenge.
Clifford
J J
JJ
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Usiello
A
A
Vallone
D
D
Kinsella
A
A
Borrelli
E
E
Waddington
J L
JL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*; D010627:Phenethylamines / Q000494:pharmacology; D010641:Phenotype; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics*
D018491:Dopamine Agonists; D010627:Phenethylamines; D017448:Receptors, Dopamine D2; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride