Effects of D1 and D2 dopamine antagonists on behavior of polydipsic rats

The behavioral and neurochemical effects of SCH3390 (SCH), a dopamine (DA) D1 antagonist, and haloperidol (HAL), a DA D2 receptor antagonist, on schedule-induced polydipsia (SIP) were examined. Once animals were made polydipsic, a vehicle or one of three doses of SCH or HAL were administered to seven groups of rats in a series of three five-session blocks in a drug condition, no-drug condition, drug condition design. Detailed behavioral measures and brain regional levels of monoamine neurotransmitters and their major acidic metabolites were analyzed. The volume of water consumed and the percent of time spent drinking was reduced dose dependently by both SCH and HAL. As drinking decreased, the time spent chewing increased for both drugs. The total amount of time animals engaged in all oral behaviors was not changed, suggesting that chewing was substituted for drinking. Neurochemical analysis revealed that HAL increased striatal DA significantly. The polydipsic paradigm may be an advantageous model for examining neuroleptics due to SIP's sensitivity to extrapyramidal side effects.