Comparative, topographically-based evaluation of behavioural phenotype and specification of D(1)-like:D(2) interactions in a line of incipient congenic mice with D(2) dopamine receptor 'knockout'.
Phenotypes were assessed topographically in mice lacking functional D(2) dopamine receptors ['knockouts'], using an ethologically based approach to assess all behaviours in the natural repertoire. D(2)-null mice evidenced an ethogram characterised initially by modest reductions in locomotion and shifts in rearing topographies. Subsequently, topographies of behaviour habituated similarly for wildtypes and 'knockouts'. Following challenge with the D(2)-like agonist RU 24213, both inhibition of rearing at a lower dose and induction of stereotyped sniffing and ponderous locomotion at higher doses were essentially absent in D(2)-null mice. Following challenge with the D(1)-like agonist A 68930, vacuous chewing was released in D(2)-null mice. This topographical approach to phenotypic characterisation implicates: (i) the D(2) receptor in these D(2)-like agonist effects and in oppositional D(1)-like: D(2)-like interactions; and (ii) the operation of material compensatory processes consequent to the developmental absence of D(2) receptors which are able to maintain ethological function under tonic, 'naturalistic' conditions but not under 'phasic' challenge.
Clifford
J J
JJ
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Kinsella
A
A
Tighe
O
O
Rubinstein
M
M
Grandy
D K
DK
Low
M J
MJ
Croke
D T
DT
Waddington
J L
JL
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D006120:Grooming / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology; D010641:Phenotype; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000502:physiology*
D002839:Chromans; D018491:Dopamine Agonists; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; C065380:A 68930