Schedule-Induced Polydipsia: Searching for the Endophenotype of Compulsive Behavior
World Journal of Neuroscience
The development of excessive and persistent drinking under intermittent food-reinforcement schedules, known Schedule-induced polydipsia (SIP), has been proposed as a successful animal model to study compulsive behaviors. On the last decade, we have been working in our laboratory on the stratification of the compulsive rats on SIP in order to know whether differences in the acquisition of compulsive drinking behavior could predict alterations in other behavioral measures as well as in the
... ll as in the neurochemical function typically associated with compulsive spectrum disorders. The aim of this review is to collate the main findings relevant to the characterization and use of the high compulsive drinking rats (HD) in SIP as a possible compulsive endophenotype. The review of the genetic, behavioral and neurochemical differences found in the selection allows us to conclude that HD rats could be a valid model for studying the compulsive phenotype and modelling psychopathology common to a variety of compulsivity spectrum disorders such as obsessivecompulsive disorder (OCD), schizophrenia and alcohol abuse. Keywords Compulsivity, Endophenotype, Schedule-Induced Polydipsia, Obsessive-Compulsive Disorder, Schizophrenia * Corresponding author. P. Flores et al. 254 most characteristic clinical examples of compulsivity; however this behavior is also present across different neuropsychiatric disorders, such as attention deficit-hyperactivity disorder (ADHD), schizophrenia, depression, compulsive gambling, eating disorders and substance abuse  . Furthermore, compulsivity is also present in excoriation and binge-eating disorder, both of which have been recently categorised as such in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders  . Because of its characteristics of "excessiveness" and "persistence" schedule-induced polydipsia (SIP), has been presented as an useful model to study those neuropsychiatric disorders characterized by the presence of compulsive behavior such as OCD (see for review  ), schizophrenia   and alcohol abuse -. Schedule-induced polydipsia can then be defined as the excessive drinking developed by food-deprived animals exposed to intermittent food-reinforcement schedules  . The drinking behavior displayed on SIP is not related to regulatory needs, given that the animals are not water deprived and there is no arranged contingency between drinking and food delivery. An excessive non-regulatory drinking, non-related to homeostatic needs or a physiological cause, has also been observed in humans among different psychiatric disorders sharing impulsive-compulsive symtomatology such as OCDs, schizophrenia and ADHD -  . Schedule-induced polydipsia has been proposed as the prototype of adjunctive behavior, a category of behavior that would include all activities occurring in reinforcement schedules with no direct relationship to reinforcement delivery  . A main characteristic of schedule-induced polydipsia is the bitonic relation between the amount of drinking and inter-reinforcement interval length  . The phenomenon of adjunctive behavior has been documented in different animal species, including humans, and with different reinforcement schedules and types of reinforcers . Other behaviors have been shown to be functionally similar to schedule-induced polydipsia, including aggression , excessive running , induced stereotypy  and pica . Although different factors, such as the state of food deprivation or the inter-food interval length influence the SIP acquisition and expression     data from our laboratory have shown that the optimal Fixed Time (FT) intervals for inducing a high rate of drinking are FT-30s  and FT-60s . Pre-existing differences among individuals have been observed in schedule-induced polydipsia (see Figure 1 ). However, those differences are not related to regulatory drinking intake, as shown by the lack of differences in water intake between HD (high drinkers) and LD (low drinkers) in home cages during 24 hours and during 1 hour after 23 hours of water restriction (see Figure 2) . Several experiments have shown that not all rats, although identical in strain, sex and age, submitted to the same conditions develop adjunctive drinking, and among those animals that do develop it, considerable individual differences in the amount of fluid intake and licks have been found -  . The aim of this review is to collate the main findings relevant to the characterization and use of the high compulsive drinking rats (HD) in SIP as a possible compulsive endophenotype. To achieve that objective we review the genetic, behavioral and neurochemical differences found by the stratification of rats according to individual differences in the acquisition of compulsive drinking on SIP.