Haloperidol both prevents and reverses quinpirole-induced nonregulatory water intake, a putative animal model of psychogenic polydipsia.
BACKGROUND
Polydipsia is a severe complication of long-term schizophrenia and, despite its unknown pathogenesis, is empirically treated with typical or atypical antipsychotics. In the rat, nonregulatory water intake is induced by repeated administration of amphetamine-like compounds or by the D2/3 agonist, quinpirole.


OBJECTIVE
This study is aimed at determining the potential activity of antipsychotic compounds with different affinities for D2 receptors in preventing and/or reversing quinpirole-induced polydipsia.


METHODS
Male Sprague-Dawley rats were treated with five injections of quinpirole (0.5 mg/kg i.p.) to induce polydipsia. The oral effects of haloperidol, olanzapine, clozapine, and ST2472 on QNP-induced polydipsia were analyzed in the following two schedules. In the preventive schedule, haloperidol (0.2, 0.4, and 0.8 mg/kg), olanzapine (1.5, 3, and 6 mg/kg), ST2472 (1 and 2 mg/kg), and clomipramine (5, 10, and 20 mg/kg) were given in combination with quinpirole from day 1 to day 5. In the reversal schedule, rats showing quinpirole-induced polydipsia on the third day received haloperidol (0.4 mg/kg), olanzapine (1.5 and 3 mg/kg), clozapine (10, 20, and 40 mg/kg), ST2472 (1, 2, 5, and 10 mg/kg), and clomipramine (5, 10, and 20 mg/kg) before quinpirole on days 4 and 5.


RESULTS
Haloperidol both prevented and reversed quinpirole-induced polydipsia, whereas olanzapine and ST2472 only reversed it. Clomipramine prevented but did not reverse quinpirole-induced polydipsia, and clozapine did not reverse it either.


CONCLUSIONS
We suggest that, once developed, polydipsia is governed by dopaminergic D2 mechanisms. In contrast, either an increase in the serotoninergic tone or an inhibition of D2 receptors can modulate the development of quinpirole-induced excessive drinking.
Amato
Davide
D
Department of Human Physiology and Pharmacology "Vittorio Erspamer", University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185, Rome, Italy.
Stasi
Maria Antonietta
MA
Borsini
Franco
F
Nencini
Paolo
P
D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D002997:Clomipramine / Q000008:administration & dosage / Q000494:pharmacology; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000077152:Olanzapine; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology
C530482:9-piperazin-1-ylpyrrolo(2,1-b)benzothiazepine; D014150:Antipsychotic Agents; D010879:Piperazines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D013841:Thiazepines; D001569:Benzodiazepines; D019257:Quinpirole; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine; D002997:Clomipramine