Effects of inactivation of D1 dopamine receptors on stereotypic and thermic responses to quinpirole (LY 171555).
The purpose of the present study was to investigate reports that the expression of dopamine agonist-induced behaviours is dependent upon the ratio of D1 to D2 receptor activation. Selective inactivation of the D1 dopamine receptor was achieved using the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while D2 receptors were maintained at control levels by the use of a D2 antagonist, raclopride. Stereotypic and hypothermic responses to quinpirole (LY 171555) were assessed and related to striatal D1 and D2 receptor concentrations. Results showed that the incidence of stereotyped sniffing behaviour induced by LY 171555 was reduced in parallel with D1 receptor loss and sniffing behaviour was abolished at low D1 receptor (less than 40% of control) concentrations. Hypothermic responses to LY 171555 were unaffected by D1 receptor loss. These findings suggest that activation of D1 receptors is a critical component of stereotypic, but not hypothermic, responses to LY 171555, the magnitude of the sniffing response being positively associated with D1 receptor concentration.
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Department of Clinical Pharmacology, School of Medicine, Flinders University of South Australia, S.A. Australia.
Crocker
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AD
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D019257:Quinpirole; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D020891:Raclopride