Effect of clozapine upon schedule-induced polydipsia (SIP) resembles neither the actions of dopamine D1 nor D2 blockade.
The effects of clozapine (CLOZ) upon acquired schedule-induced polydipsia in rats were compared to the effects of the dopamine (DA) D1 antagonist SCH 23390 (SCH) and the DA D2 antagonist raclopride (RAC). All three compounds suppressed water consumption, but only SCH and RAC decreased drinking efficiency. SCH was the only compound with an effect on panel pressing (PP), causing suppression even at a dose without effect upon water intake. SCH also affected the temporal pattern of licking (TPL) at all doses, while clozapine, 10 mg/kg, only affected the pattern acutely, and raclopride was without effect. In conclusion, PP and the TPL are more sensitive to D1 than D2 blockade. While PP and the TPL are more sensitive than water intake to D1 blockade, the opposite is true for D2 blockade. It is possible to differentiate between DA D1/D2 antagonists and CLOZ in this model, focusing upon reduction in water consumption, with and without reduction in drinking efficiency. Furthermore, it is possible to differentiate between D1 and D2 blockade by analyzing water consumption, PP and the TPL.
Department of Psychopharmacology, St Hans Hospital, Roskilde, Denmark.
M
M
Didriksen
G M
GM
Olsen
A V
AV
Christensen
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003864:Depression, Chemical; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004327:Drinking Behavior / Q000187:drug effects*; D008297:Male; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D020891:Raclopride; D003024:Clozapine