Applications of schedule-induced polydipsia in rodents for the study of an excessive ethanol intake phenotype

Abstract

Schedule-induced polydipsia (SIP) is generated by subjecting a highly motivated animal to a sub-optimal rate of food reinforcement while also providing access to a fluid. SIP is one of several adjunctive (or displacement) behaviors that are expressed in an exaggerated form that is deemed ‘excessive’. This feature makes SIP an attractive model for studying an excessive ethanol drinking phenotype in rodents. Multiple experimental variables are crucial for the full manifestation of adjunctive drinking, including the degree of food deprivation, the inter-pellet interval selected, and the size of the food reward offered. Although these variables were extensively studied and optimized for water polydipsia in rats, a similarly customized approach to ethanol SIP and application of the procedure in mice have largely been curtailed in favor of the default variable values historically used for water SIP in rats. Further, ethanol SIP also requires careful consideration of variables such as taste and ethanol concentration. Investigation of the stress axis and neurochemical systems such as dopamine and serotonin in mediating adjunctive drinking stemmed from two leading hypotheses regarding the underlying mechanisms of SIP generation: 1) SIP as a coping strategy to mitigate stress associated with the aversive environmental condition, and 2) SIP as a displacement of reward in a highly motivated animal. Ethanol SIP is a powerful model of excessive intake because it can generate an ethanol-dependent state and sustain frequent and intoxicating levels of blood ethanol with voluntary oral consumption. The required food deprivation and the loss of the excessive drinking phenotype following removal of the generator schedule are the two main limitations of the model. Future utility of ethanol SIP will be enhanced by more fully dissecting the underlying hormonal and neurochemical mechanisms and optimizing experimental variables for ethanol SIP on a per species and strain basis.

Rat animal models for screening medications to treat alcohol use disorders

“…In order to get a rodent to consume sufficient amounts of ethanol, experimental manipulations are required. These experimental/environmental manipulations include fluid deprivation (Sandi et al, 1990), schedule-induced polydipsia (Ford, 2014; Meisch, 1975, 2001), scheduled availability (Holloway et al, 1984) including intermittent every-other-day access (Carnicella et al, 2014), sucrose-fading (Samson, 1986), and/or forced induction of dependence (Deutsch and Eisner, 1977); which can be achieved intragastrically (Crews, 2008; French, 2001), intraperitoneally (Pascual et al, 2009, 2014), by ethanol-vapor exposure (Roberts et al, 2000; Vendruscolo and Roberts, 2014), chronic drinking of a liquid ethanol diet (Brown et al, 2004; Lieber and DeCarli, 1989), or long-term drinking with water and food concurrently available (Vengeliene et al, 2009). Most of these methods include an integral stress factor, which does have some face validity with the clinical condition (Al’Absi, 2007).…”

Effects of shifts in food reinforcement context on rats’ consumption of concurrently available water or sucrose solution

“…It was predicted that the negative incentive shift would provoke more drinking than the other transitions and that there would be marked increases in fluid consumption when tap water was replaced with the sucrose solution. Additionally, of some interest was to determine if negative incentive shifts produce schedule-induced polydipsia (SIP), the classic example of adjunctive behavior (for a review, see Ford, 2014). If the transitions produce polydipsia, excessive drinking without a biological need, we would expect consumption to exceed three times the amount that would be consumed in the absence of testing, as has been demonstrated with SIP (Falk, 1961(Falk, , 1966(Falk, , 1969(Falk, , 1971Falk & Tang, 1988).…”

Voluntary Binge Consumption of Ethanol in a Sweetened, Chocolate-Flavored Solution by Male and Female Adolescent Sprague Dawley Rats

“…Here, we report our first steps to create a model of adolescent voluntary EtOH intake that produces binge‐like BEC levels in outbred Sprague Dawley rats after a short daily limited access period. Our initial strategy was to assess adolescent EtOH intake using schedule‐induced polydipsia (SIP) (Falk, , ), a procedure that has been used to induce excessive alcohol intake in food deprived adult rodents by providing continuous EtOH access during sessions where food access is provided only intermittently (for review, see Ford, ). For instance, using moderate food deprivation and scheduled delivery of small food pellets along with unlimited session access first to water and then increasing concentrations of EtOH over multiple weeks, Falk and colleagues () ultimately produced BECs averaging 100 mg/dl in adult rats, with peak BECs in the 150 to 300 mg/dl range.…”

“…For instance, using moderate food deprivation and scheduled delivery of small food pellets along with unlimited session access first to water and then increasing concentrations of EtOH over multiple weeks, Falk and colleagues () ultimately produced BECs averaging 100 mg/dl in adult rats, with peak BECs in the 150 to 300 mg/dl range. Despite recent renewed interest in SIP as a model of excessive alcohol consumption (see Ford, ; Ford et al., , ; Moreno and Flores, ), this means for induction of high alcohol consumption has received little, if any, exploration in adolescent animals. Although adolescence is a notably shorter period than the amount of time used to implement SIP by Falk and colleagues (), our goal was to modify the SIP procedure by providing EtOH in a highly palatable vehicle solution in an attempt to induce high adolescent EtOH intakes.…”