Schedule-induced Polydipsia in Lines of Rats Selectively Bred for High and Low Ethanol Preference

Abstract

Ethanol drinking was assessed in the P/NP, HAD1/LAD1, and HAD2/LAD2 lines of rats under environmental conditions that produce schedule-induced polydipsia. Female rats (n = 8/line), maintained at 85% of free-feeding body weights, underwent daily 1-h sessions during which 45-mg food pellets were delivered every 60 s. Water, 2, 4, 8, 16, or 32% w/v ethanol solution was available from a single bottle for 8 consecutive sessions at each concentration, with blood-ethanol levels (BELs) determined after selected sessions. P and HAD2 rats drank more water and ethanol than their non-preferring counterparts, while HAD1 and LAD1 rats did not differ. Ethanol intake and BELs were positively correlated (r = 0.75) across lines. Finally, rats were allowed 14 daily choice sessions with 8% ethanol and water concurrently available. Water intake generally exceeded ethanol intake in all lines, while P rats drank similar amounts of both fluids. These line differences indicate pleiotropic effects of genes that mediate ethanol intake and schedule-induced behaviors. KeywordsAdjunctive behavior; Schedule-induced polydipsia; Alcohol-preferring rats; Alcohol-nonpreferring rats; Genetic correlation; P rats; NP rats; HAD rats; LAD rats It is well accepted that alcoholism is a complex behavioral genetic trait accounted for by the interaction effects of multiple genes and environmental factors (Crabbe 2002;Enoch and Goldman 2001). A useful approach to the development of an animal model of the genetic contribution to alcohol drinking has been the development of programs in which rats are selectively bred for extremes of high and low voluntary oral alcohol consumption (Lumeng et al. 1995). Perhaps the most powerful, albeit controversial, animal model of the contribution of environmental factors to excessive alcohol drinking is drinking engendered by scheduleinduced polydipsia (Falk 1998). The purpose of the present investigation is to study geneenvironment interactions by examining alcohol drinking by selectively bred rats under conditions that produce schedule-induced polydipsia.The alcohol-preferring (P) and-nonpreferring (NP) lines were developed at Indiana University through bidirectional selective breeding from a randomly bred closed colony of Wistar rats from the Walter Reed Army Institute of Research, Washington, D.C. (Lumeng et al. 1977;Li et al. 1991). The selection criterion for P rats is intake greater than 5 g ethanol/kg body weight/ day and the selection criterion for NP rats is intake less than 1.5 g ethanol/kg body weight/day with 10% (v/v) ethanol, water, and food continuously available (Lumeng et al. 1977 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript rats have characteristics important for an animal model of alcoholism (Cicero 1979). Voluntary oral consumption of ethanol by P rats results in high blood ethanol concentrations (50-250 mg %) even in the presence of food and water (Murphy et al. 1986). P rats consume ethanol for its pharmacological effects rather than its taste, smell or caloric co...

Compulsive drug use and its neural substrates

“…For example, excessive alcohol consumption and alcohol dependence is associated with gene and protein expression changes in the amygdala (Bell et al, 2006;Rodd et al, 2007;Contet et al, 2011). Further, increasing NPY levels in the CeA or CRF antagonism in the CeA abolished dependenceinduced increases in alcohol intake (Funk et al, 2006(Funk et al, , 2007Thorsell et al, 2007;Gilpin et al, 2008a,b), whereas these treatments were without effect in non-dependent rats (Katner et al, 2002;Funk et al, 2007;Gilpin et al, 2008c;Henderson et al, 2010). Although studied most widely for alcohol, these findings also extend to other drugs of abuse.…”

Schedule-induced polydipsia as a model of compulsive behavior: neuropharmacological and neuroendocrine bases

“…The comparison between the Lister Hooded strain and Wistar rats also yielded some differences in which Wistar animals more readily acquired SIP and Selection based on drank above 10 ml Drinkers vs non-drinkers Eat and drink in response to electrical stimulation of lateral hypothalamus Valenstein (1984, 1985) SIP positive vs negative rats ↑ Prolactin levels Dantzer et al (1988a) Learn faster an active avoidance task ↓ freezing in a defeat test Dantzer et al (1988b) SIP-positive vs SIP-negative rats ↑ Prolactin levels Dantzer et al (1988a) exhibited a greater level of water drinking (Cardona et al 2009). The SIP behavior may work additively with genetic susceptibilities for ethanol drinking, as evidenced in three rat lines selectively bred for high and low ethanol preference that showed differences in SIP behavior, indicating possible genetic correlations between the selected traits in these lines of rats and behavioral traits indicative of susceptibility to SIP (Gilpin et al 2008). Moreover, selective breeding for Roman high-(RHA) and low-avoidance (RLA) rats for rapid vs. extremely poor acquisition of active avoidance behavior in a shuttle box resulted in two phenotypes that included differences in sensation/novelty seeking, anxiety/fearfulness, stress responsivity, and susceptibility to addictive drugs (Driscoll et al 1998;Escorihuela et al 1997Escorihuela et al , 1999Fattore et al 2009).…”

“…Other behaviors have been shown to be functionally similar to SIP in terms of schedule induction, including aggression and escape (Looney and Cohen 1982), excessive running (Collier and Levitsky 1968), induced stereotypy (Mittleman et al 1991), and pica (Wilson and Cantor 1987;Falk 1971). Moreover, in SIP, the substitution of water for ethanol solution-induced equivalent levels of consumption has been considered as a promising behavioral model of alcohol abuse, relating directly to the induction of compulsive alcohol drinking (Gilpin et al 2008;Mittleman et al 2003Mittleman et al , 2011Singer et al 1982;Singer and Wallace 1984;Wayner 2002). Schedule induction and ethanol polydipsia provide an opportunity to investigate the development of drinking typologies that lead to chronic, excessive voluntary alcohol consumption in animals (Colotla 1981;Falk and Tang 1988), as well as the neural substrates and pharmacology of alcohol addiction (Escher and Mittleman 2006;Mittleman et al 2011).…”

“…Because of its characteristics of "excessiveness" and "persistence," growing evidence points to schedule-induced polydipsia (SIP) as a candidate model for the study of neuropsychiatric disorders presenting with compulsive behavior such as OCD, schizophrenia (Hawken et al 2011;Rosenzweig-Lipson et al 2007;Schechter et al 2008;Woods-Kettelberger et al 1997; for review, see Platt et al 2008), and alcohol abuse (Gilpin et al 2008;Mittleman et al 2003Mittleman et al , 2011Wayner 2002). The SIP model is characterized by the development of an adjunctive behavior of excessive drinking in food-deprived animals exposed to intermittent food-reinforcement schedules (Falk 1961(Falk , 1971.…”

Impulsivity Characterization in the Roman High- and Low-Avoidance Rat Strains: Behavioral and Neurochemical Differences

“…Moreover, the SIP model seems to be sensitive to detect susceptibilities in individuals to addictive behavior (Gilpin et al, 2008;Mittleman et al, 2003;Toscano et al, 2008) and bingeeating behavior (Moreno et al, 2009). Curiously and relevant to this work, these disorders also share impulsivity as one of the main symptoms (American Psychiatric Association, 2000).…”