Influence of reinforcement schedule on ethanol consumption patterns in non-food restricted male C57BL/6J mice

Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Alcohol (Impact Factor: 2.01). 03/2007; 41(1):21-9. DOI: 10.1016/j.alcohol.2007.02.003
Source: PubMed


Ethanol reinforcement should ideally be evaluated in animals that are not food deprived to ensure that the motivation behind its consumption is pharmacological, and not caloric, in nature. The objective of this work was to assess the influence of reinforcement schedule on ethanol intake in nondeprived mice. Male C57BL/6J mice were trained to respond on an ethanol-reinforced lever on a fixed ratio 4 reinforcement schedule for 10% ethanol (10E). The appetitive and consummatory phases were then procedurally separated by changing the response requirement (RR), so that mice were permitted 30-min continuous 10E access after completion of either four (RR4) or eight (RR8) responses. Phase separation yielded a heightened appetitive drive to acquire 10E access (as indexed by a significant decrease in the latency to first active lever and a trend toward a decrease in the latency to first sipper contact) and an augmented level of drinking (twofold elevation in the ethanol dose consumed). Robust extinction responding on the ethanol-appropriate lever indicated that ethanol was effective as a behavioral reinforcer. These results suggest that the separation of appetitive and consummatory phases of ethanol self-administration may prove useful in future evaluations of the pharmacological and genetic bases of ethanol reinforcement in mice.

Download full-text


Available from: Gregory Mark, Jul 16, 2014
11 Reads
  • Source
    • "Studies also have shown mice responding for ethanol when ethanol reinforcement is continuously available (Risinger, Brown, Doan, & Oakes, 1998), when it is made available for extended periods (w16 h) (Besheer, Lepoutre, & Hodge, 2004; Hodge et al., 2006), and when access is limited for short periods of time (w30e60 min) (Chu et al., 2007; Lopez, Anderson, & Becker, 2008; Lopez & Becker, 2014; Ramaker, Strong, Ford, & Finn, 2012; Sparta et al., 2009; Tsiang & Janak, 2006). Using the 'sipper' model described above, mice were shown to reliably respond to gain access to drink ethanol from a bottle made available for 30 min once the response requirement was satisfied (Finn et al., 2008; Ford et al., 2007). In this latter case, manipulating the reinforcement schedule to further separate the appetitive and consummatory components of the procedure enhanced both the appetitive drive to gain access to ethanol (as indicated by reduced latency to fulfill the response requirement) and the consummatory component (increased amount of ethanol consumed). "
    [Show abstract] [Hide abstract]
    ABSTRACT: While rats have been predominantly used to study operant ethanol self-administration behavior in the context of dependence, several studies have employed operant conditioning procedures to examine changes in ethanol self-administration behavior as a function of chronic ethanol exposure and withdrawal experience in mice. This review highlights some of the advantages of using operant conditioning procedures for examining the motivational effects of ethanol in animals with a history of dependence. As reported in rats, studies using various operant conditioning procedures in mice have demonstrated significant escalation of ethanol self-administration behavior in mice rendered dependent via forced chronic ethanol exposure in comparison to nondependent mice. This paper also presents a summary of these findings, as well as suggestions for future studies.
    Alcohol (Fayetteville, N.Y.) 05/2014; 48(3). DOI:10.1016/j.alcohol.2014.02.002 · 2.01 Impact Factor
  • Source
    • "One advantage in the use of the " sipper " procedure is that the appetitive and consummatory phases of ethanol self-administration can be procedurally separated (e.g., Samson et al., 1998, 2000), which allows for an examination of drug effects on each phase of ethanol selfadministration . Importantly, we have documented in C57BL/6 mice that phase separation yielded a heightened appetitive drive to acquire ethanol access and more than a two-fold increase in ethanol consumption, when compared with responding on a FR schedule (Ford et al., 2007a). Thus, the higher ethanol self-administration in C57BL/6 mice performing on a RR versus a FR schedule was an additional advantage in the use of the " sipper " procedure in the present studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Drinking to intoxication or binge drinking is a hallmark characteristic of alcohol abuse. Although hard to model in rodents, the scheduled high alcohol consumption (SHAC) procedure generates high, stable ethanol intake and blood ethanol concentrations in mice to levels consistent with definitions of binge drinking. The purpose of the present studies was to determine the effects of pharmacological manipulation of the opioidergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic systems on binge drinking with the SHAC procedure. Parallel manipulations were conducted in mice trained in operant self-administration of either sucrose or ethanol. For the SHAC procedure, genetically heterogeneous Withdrawal Seizure Control mice were given varying periods of fluid access, with a 30-min ethanol session every third day (total of seven). Mice were pretreated intraperitoneally with naltrexone (0, 0.6, or 1.25 mg/kg), baclofen (0, 2.5, or 5.0 mg/kg), or 2-methyl-6-(phenylethynyl)-pyridine (MPEP; 0, 3.0, or 10.0 mg/kg) before each ethanol session. For the operant self-administration procedure, separate groups of C57BL/6 mice were trained to complete a single response requirement (16 presses on the active lever) to gain 30 min of access to an ethanol or a sucrose solution. Mice received pretreatments of the same doses of naltrexone, MPEP, or baclofen before the self-administration sessions, with saline injections on intervening days. Naltrexone produced a dose-dependent decrease in binge drinking, and the highest dose also significantly decreased operant self-administration of ethanol and sucrose. Both doses of baclofen significantly decreased binge alcohol consumption, but the higher dose also tended to decrease water intake. The highest dose of baclofen also significantly decreased operant self-administration of sucrose. MPEP (10 mg/kg) significantly decreased binge alcohol consumption and sucrose self-administration. These results indicate that manipulation of the opioidergic, glutamatergic, and GABAergic systems significantly decreased binge drinking.
    Alcohol (Fayetteville, N.Y.) 02/2011; 45(1):33-44. DOI:10.1016/j.alcohol.2010.07.009 · 2.01 Impact Factor
  • Source
    • "However, when a schedule was imposed (RR8) that allowed mice to regulate their own rate of 10E consumption for 30 uninterrupted minutes, WSR mice significantly increased their 10E intake by 76% over the intake in WSP mice (Figure 3). Notably, the enhancement of drinking in WSR mice following a schedule manipulation from FR4 to RR8 is similar to our recent results in male C57BL/6 mice, where transition from a FR4 to a RR4 schedule of reinforcement was associated with a doubling of the ethanol dose consumed during a 30 min session (Ford et al., 2007a). Although BECs were not measured, WSR mice were consuming a dose of ethanol (0.8 g/kg) within 30 minutes that has previously been shown to produce BECs ≥ 50 mg/dl (or 10.9 mM; e.g., Elmer et al., 1987;Czachowski et al., 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several meta-analyses indicate that there is an inverse genetic correlation between ethanol preference drinking and ethanol withdrawal severity, but limited work has characterized ethanol consumption in 1 genetic animal model, the Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mouse lines selected for severe or mild ethanol withdrawal, respectively. We determined whether line differences existed in: (i) operant self-administration of ethanol during sucrose fading and under different schedules of reinforcement, followed by extinction and reinstatement of responding with conditioned cues and (ii) home cage drinking of sweetened ethanol and the development of an alcohol deprivation effect (ADE). Withdrawal Seizure-Prone-1 mice consumed more ethanol than WSR-1 mice under a fixed ratio (FR)-4 schedule as ethanol was faded into the sucrose solution, but this line difference dissipated as the sucrose was faded out to yield an unadulterated 10% v/v ethanol solution. In contrast, WSR-1 mice consumed more ethanol than WSP-1 mice when a schedule was imposed that procedurally separated appetitive and consummatory behaviors. After both lines achieved the extinction criterion, reinstatement was serially evaluated following oral ethanol priming, light cue presentation, and a combination of the 2 cues. The light cue produced maximal reinstatement of responding in WSP-1 mice, whereas the combined cue was required to produce maximal reinstatement of responding in WSR-1 mice. There was no line difference in the home cage consumption of a sweetened ethanol solution over a period of 1 month. Following a 2-week period of abstinence, neither line developed an ADE. Although some line differences in ethanol self-administration and reinstatement were identified between WSP-1 and WSR-1 mice, the absence of consistent divergence suggests that the genes underlying these behaviors do not reliably overlap with those that govern withdrawal severity.
    Alcoholism Clinical and Experimental Research 11/2010; 35(2):326-37. DOI:10.1111/j.1530-0277.2010.01348.x · 3.21 Impact Factor
Show more