Effects of Risperidone on the Schedule-Induced Polydipsia in Rats

Lee, Gi Chul; Lee, Jung Ho; Yoon, Doh Joon; Choi, Young Min; Jeon, Seong Ill; Kim, Tae Soo; Jeong, Hong Kyung; Ha, Jun Myung; Jeong, Jae Hyun

Abstract

OBJECTIVES
This study was designed to evaluate the effects of risperidone on the schedule-induced polydipsia (SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered risperidone as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol as a dopamine antagonist to rats which showed schedule-induced polydipsic behaviour.
METHODS
Sprage-Dawley rats weighing 200 - 250gm were individually housed and main-tained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds (FT 60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior (greater than 3 times of water per session on average). 5 groups of rats were administered risperidone (0.1mg/kg, i.p), risperidone (0.5mg/kg, i.p), fluoxetine (5mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.), and vehicle (1cc/kg, i.p. ) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats (N=8) was individually housed and given a single bolus (14.5gm) of food per day which maintained them at their average body weight.
RESULTS
The results were as follows; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1mg group and the risperidone 0.5mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsic water intakes. 3) The fluoxetine group (22.5+/-10.4ml) showed significantly lower amounts of water intake than haloperidol group (41.3+/-7.1ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.8+/-3.5ml) showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) and the vehicle control (34.4+/-6.8ml) at 3rd weeks of drug treatment. The risperidone 0.1mg group and the risperidone 0.5mg group showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) at 2nd weeks and the vehicle control (37.5+/-12.5 , 34.4+/-6.8ml) at 2nd and 3rd weeks of drug treatment.
CONCLUSIONS
Above findings suggest that the fixed time feeding procedure for schedule induced polydipsia could be applied as an effective animal model of obsessive compulsive disorder for the evaluation of pharmacological challenge study. We confirmed that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the schedule-induced polydipsic behaviour but the onset of effect was later than fluoxetine.