Dependence induced increases in intragastric alcohol consumption in mice

Abstract

Three experiments used the Intragastric Alcohol Consumption (IGAC) procedure to examine effects of variations in passive ethanol exposure on withdrawal and voluntary ethanol intake in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2). Experimental treatments were selected to induce quantitative differences in ethanol dependence and withdrawal severity by: (a) varying the periodicity of passive ethanol exposure (3, 6 or 9 infusions/day), (b) varying the dose per infusion (Low, Medium or High), and (c) varying the duration of passive exposure (3, 5 or 10 days). All experiments included control groups passively exposed to water. B6 mice generally self-infused more ethanol than D2 mice, but passive ethanol exposure increased IGAC in both strains, with D2 mice showing larger relative increases during the first few days of ethanol access. Bout data supported the characterization of B6 mice as sippers and D2 mice as gulpers. Three larger infusions per day produced a stronger effect on IGAC than six or nine smaller infusions, especially in D2 mice. Increased IGAC was strongly predicted by cumulative ethanol dose and intoxication during passive exposure in both strains. Withdrawal during the passive exposure phase was also a strong predictor of increased IGAC in D2 mice. However, B6 mice showed little withdrawal, precluding analysis of its potential role. Overall, these data support the hypothesis that dependence-induced increases in IGAC are jointly determined by two processes that might vary across genotypes: (a) tolerance to aversive post-absorptive ethanol effects, and (b) negative reinforcement (i.e., alleviation of withdrawal by self-administered ethanol).

Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence

“…The sipper tubes were connected to lickometers (ENV-250B, Med Associates) interfaced to a computer that stored lick totals and number of infusions automatically every 5 min using LabVIEW™ 6.1 software (National Instruments, Austin, TX, USA). Additional apparatus details can be found elsewhere (Fidler et al, 2012). …”

“…Continuous and intermittent ethanol vapor exposure has been shown to reliably produce signs of dependence (e.g., Schulteis et al, 1995; 1996; Macey et al, 1996; Becker et al, 2000), to increase alcohol drinking and operant self-administration of alcohol (e.g., Becker and Lopez, 2004; O'Dell et al, 2004; Finn et al, 2007; Gilpin et al, 2009), and to increase alcohol self-administration to alleviate withdrawal symptoms (Roberts et al, 1996) and during a period of protracted abstinence (Roberts et al, 2000). More recently, the intragastric alcohol consumption (IGAC) model has shown increased alcohol self-administration in dependent mice given ethanol access during acute alcohol withdrawal (Fidler et al, 2012; Cunningham et al, 2013). …”

“…The current study tested the ability of two ghrelin receptor antagonists (GHSR1a), DLys and JMV2959, to decrease alcohol drinking across three procedures: 1) alcohol drinking after chronic intermittent ethanol vapor exposure in C57BL/6J mice (Finn et al, 2007); 2) intragastric (IG) alcohol self-infusion after passive IG alcohol infusions in C57BL/6J mice (Fidler et al, 2012); and 3) progressive ratio (PR) operant alcohol self-administration in Wistar rats after chronic intermittent ethanol vapor (O'Dell et al, 2004). These subjects and models were chosen to provide a wide array of examinations to test the effectiveness of ghrelin antagonists and their interaction with alcohol drinking.…”

Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment

“…Current preclinical models used to induce alcohol dependence in both rats and mice include involuntary/forced exposure to ethanol through vapor, intragastric intubation, or liquid diet (Braconi et al, 2010; Fidler, Clews, & Cunningham, 2006; Fidler et al, 2012; Gilpin, Misra, & Koob, 2008; Gilpin et al, 2009; Kurokawa, Mizuno, & Ohkuma, 2013; Macey, Schulteis, Heinrichs, & Koob, 1996; O’Dell, Roberts, Smith, & Koob, 2004). Each procedure has advantages and disadvantages.…”

Frameworks of Alcohol Addiction

“…High doses of alcohol solution will also be selfadministered intragastrically in mice and rats after the animals are made dependent via passive intragastric infusion (Fidler, Clews, & Cunningham, 2006;Fidler et al, 2012). Here, the rats will self-infuse 4-7 g/kg per day of ethanol, and blood alcohol levels average 0.12 g%, measured 30 minutes after the start of a bout in which rats infuse 1.5 g/kg every 30 minutes.…”