A review of the neuropharmacological profile of schedule‐induced polydipsia

Schedule-induced polydipsia (SIP) arises when subjects consume excessive amounts of water during interval responding on operant tasks, a paradigm introduced and mostly developed in rats. Neuropharmacological studies conducted on SIP have mainly shown a prominent role of dopamine and 5HT in this adjunctive behavior. In particular, D₁/D₂ receptor antagonists decrease SIP, whereas low doses of dopamine reuptake blockers increase SIP. There is more specific evidence of a decline in SIP after lesions of the mesolimbic dopamine pathway. A decline in SIP is likewise observed after the injection of 5HT reuptake blockers and modulated by 5HT_2A/5HT_2C receptor agonists and antagonists. Despite more limited studies with other neurotransmitter systems, SIP has so far been shown to decline after the injection of muscarinic or NMDA receptor antagonists as well as benzodiazepine receptor agonists. Under some conditions, the role of neuroendocrine factors is shown by alterations in blood corticosterone levels during the course of SIP, indicative of its stress-reducing properties.