The effects of haloperidol and raclopride in the paw test are influenced similarly by SCH 39166.
We investigated the role of dopamine D1 and D2 receptors in the paw test, an animal model used to assess both the antipsychotic potential and extrapyramidal side effects of drugs. The dopamine D1 receptor antagonist, SCH 39166, as well as the dopamine D2 receptor antagonist raclopride, increased the hindlimb retraction time (HRT), viz. a parameter that models antipsychotic potential, at doses that were lower than those that increased the forelimb retraction time (FRT), viz. a parameter that models extrapyramidal side effects. In contrast, the same dose of haloperidol enhanced both parameters. SCH 39166 enhanced the haloperidol- and raclopride-induced effects on FRT, whereas neither haloperidol nor raclopride enhanced the SCH 39166-induced effects upon this parameter. Except at very high doses, SCH 39166 did not alter the haloperidol- and raclopride-induced effects on HRT, and vice versa. No difference between haloperidol and raclopride was found in the interaction experiments. The clinical impact of these findings is discussed.
Prinssen
E P
EP
Psychoneuropharmacological Research Unit, Catholic University of Nijmegen, Netherlands.
Ellenbroek
B A
BA
Stamatovic
B
B
Cools
A R
AR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D005552:Forelimb / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D006614:Hindlimb / Q000187:drug effects; D008297:Male; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012457:Salicylamides / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; C058081:ecopipam; D020891:Raclopride; D006220:Haloperidol